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Diagnosis and Treatment > Medication

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  • Methylprednisolone x
  • Thyroxine (T4) x
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Misaki Aoshima Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Koji Nagayama Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Kei Takeshita Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Hiroshi Ajima Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Sakurako Orikasa Departments of Endocrinology Diabetes and Metabolism, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Ayana Iwazaki ²Departments of Endocrinology Diabetes and Metabolism, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan

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Hiroaki Takatori Department of Rheumatology, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan

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Yutaka Oki Department of Family and Community Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

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Summary

Patients treated with immunosuppressive drugs, especially methotrexate (MTX), rarely develop lymphoproliferative disorders (LPDs), known as MTX-related LPD (MTX–LPD). The primary site of MTX–LPD is often extranodal. This is the first reported case of MTX–LPD in the pituitary. A 65-year-old woman was admitted to our hospital with symptoms of oculomotor nerve palsy and multiple subcutaneous nodules. She had been treated with MTX for 11 years for rheumatoid arthritis. Computed tomography showed multiple masses in the orbit, sinuses, lung fields, anterior mediastinum, kidney, and subcutaneous tissue. Brain magnetic resonance imaging revealed a sellar mass. She was diagnosed with hypopituitarism and central diabetes insipidus based on endocrine examination. Although pituitary biopsy could not be performed, we concluded that the pituitary lesion was from MTX–LPD, similar to the lesions in the sinuses, anterior mediastinum, and subcutaneous tissue, which showed polymorphic LPD on biopsy. MTX was discontinued, and methylprednisolone was administered to improve the neurologic symptoms. After several weeks, there was marked improvement of all lesions, including the pituitary lesion, but the pituitary function did not improve. When pituitary lesions are caused by MTX–LPD, the possibility of anterior hypopituitarism and central diabetes insipidus needs to be considered. Further studies are needed to investigate the effectiveness of early diagnosis and treatment of MTX–LPD in restoring pituitary dysfunction.

Learning points

  • Pituitary lesions from MTX–LPD may cause hypopituitarism and central diabetes insipidus.

  • Pituitary metastasis of malignant lymphoma and primary pituitary lymphoma, which have the same tissue types with MTX–LPD, have poor prognosis, but the lesions of MTX–LPD can regress only after MTX discontinuation.

  • In cases of pituitary lesions alone, a diagnosis of MTX–LPD may be difficult, unless pituitary biopsy is performed. This possibility should be considered in patients treated with immunosuppressive drugs.

  • Pituitary hypofunction and diabetes insipidus may persist, even after regression of the lesions on imaging due to MTX discontinuation.

Taxonomy:
Clinical Overview, Gland/Organ, Pituitary, Topic, Pituitary, Hormone, ACTH, Cortisol, FSH, IGF1, LH, Prolactin, Thyroxine (T4), Triiodothyronine (T3), TSH, Condition/ Syndrome, Diabetes insipidus - neurogenic/central, Hypopituitarism, Iatrogenic disorder, Rheumatoid arthritis, Patient Demographics, Age, Geriatric, Gender, Female, Ethnicity, Asian - Japanese, Country of Treatment, Japan, Diagnosis and Treatment, Signs and Symptoms, Diabetes insipidus, Facial palsy, Facies - abnormal, Hypopituitarism, Mydriasis, Ptosis, Splenomegaly, Investigation, ACTH, Biopsy, Cortisol, C-reactive protein, Creatinine, CT scan, FSH, FT3, FT4, Haematoxylin and eosin staining, Histopathology, IGF1, Lactate dehydrogenase, LH, MRI, Prolactin, Serum osmolality, Skin biopsy, Thyroid antibodies, TSH, Urine osmolality, Medication, Desmopressin, Methylprednisolone, Prednisolone, Thyroxine (T4), Publication Details, Case Report Type, New disease or syndrome: presentations/diagnosis/management
DOI:
https://doi.org/10.1530/EDM-19-0082
Volume/Issue:
Volume 2019: Issue 1
Open access
Beverly T Rodrigues Department of Diabetes and Endocrinology, The Townsville Hospital, Townsville, Queensland, Australia
School of Medicine and Dentistry, James Cook University, Douglas, Queensland, Australia

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Zulfiquer Otty Department of Oncology, The Townsville Hospital, Townsville, Queensland, Australia

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Kunwarjit Sangla Department of Diabetes and Endocrinology, The Townsville Hospital, Townsville, Queensland, Australia

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Vasant V Shenoy Department of Diabetes and Endocrinology, The Townsville Hospital, Townsville, Queensland, Australia
School of Medicine and Dentistry, James Cook University, Douglas, Queensland, Australia

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Summary

Autoimmune hypophysitis (AH) has been previously described in a typical demographic population, primarily women in the reproductive age group and perinatal period. The era of immune modulation using anti-cytotoxic T-lymphocyte-associated antigen 4 biological therapy (ipilimumab) against advanced cancers like metastatic melanomas has now resulted in a new form of hypophysitis being increasingly recognised under a spectrum of immune-related adverse events. Drug-related AH often presents with subtle symptoms and a pituitary mass, with the potential for fatality necessitating wide awareness and a high index of clinical suspicion given that it is usually treatable. We describe below two cases of AH within the last three months at our centre, which were treated with different regimens and produced good endocrine outcomes.

Learning points

  • AH is a new and defined clinical entity occurring as a side effect of ipilimumab, which enhances immune-mediated destruction of metastatic melanoma.

  • It can present insidiously and have life-threatening complications related to hypocortisolism, hence a high index of clinical suspicion must be exerted by treating physicians, and seems to result in resolution of pituitary masses and variable improvements of pituitary function.

  • Clinical improvement, radiological resolution of pituitary masses and variable normalisation of pituitary function are possible with early treatment with high-dose oral or i.v. steroids and hormone replacement therapy, although duration and dosing protocols are unclear at this stage.

  • Ipilimumab should continue to be prescribed as treatment for metastatic melanoma; however, close clinical observation of patient's progress must be maintained while they are on this drug.

  • Predictive factors for onset of AH remain unclear and it is imperative that AH is distinguished from pituitary metastases.

  • Further studies are required to determine the safety of continuing therapy with ipilimumab in patients who have developed AH while on treatment.

Taxonomy:
Clinical Overview, Gland/Organ, Pituitary, Topic, Pituitary, Hormone, Cortisol, TSH, Condition/ Syndrome, Autoimmune hypophysitis, Hypophysitis, Metastatic melanoma, Patient Demographics, Age, Adult, Gender, Female, Male, Ethnicity, White, Country of Treatment, Australia, Diagnosis and Treatment, Signs and Symptoms, Anorexia, Bloating, Constipation, Fatigue, Headache, Nausea, Somnolence, Weight gain, Investigation, ACTH, Cortisol (serum), FT3, FT4, MRI, Prolactin, TSH, Medication, Glucocorticoids, Hydrocortisone, Ipilimumab, Methylprednisolone, Prednisolone, Prednisone, Thyroxine (T4), Related Disciplines, Oncology, Radiology/Rheumatology, Publication Details, Case Report Type, Unique/unexpected symptoms or presentations of a disease
DOI:
https://doi.org/10.1530/EDM-14-0098
Volume/Issue:
Volume 2014: Issue 1
Open access