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Diagnosis and Treatment > Signs and Symptoms

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Hui Yi Ng Department of Clinical Medicine, Level 4, Macquarie University, 2 Technology Place, Macquarie University, New South Wales, Australia

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Divya Namboodiri Department of Clinical Medicine, Level 4, Macquarie University, 2 Technology Place, Macquarie University, New South Wales, Australia

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Diana Learoyd University of Sydney, Faculty of Medicine and Health, Northern Clinical School, Reserve Road St Leonards, New South Wales, Australia

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Andrew Davidson Department of Neurosurgery, Level 2, Macquarie University, 2 Technology Place Macquarie University, New South Wales, Australia

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Bernard Champion Department of Clinical Medicine, Level 4, Macquarie University, 2 Technology Place, Macquarie University, New South Wales, Australia

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Veronica Preda Department of Clinical Medicine, Level 4, Macquarie University, 2 Technology Place, Macquarie University, New South Wales, Australia

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Summary

Co-secreting thyrotropin/growth hormone (GH) pituitary adenomas are rare; their clinical presentation and long-term management are challenging. There is also a paucity of long-term data. Due to the cell of origin, these can behave as aggressive tumours. We report a case of a pituitary plurihormonal pit-1-derived macroadenoma, with overt clinical hyperthyroidism and minimal GH excess symptoms. The diagnosis was confirmed by pathology showing elevated thyroid and GH axes with failure of physiological GH suppression, elevated pituitary glycoprotein hormone alpha subunit (αGSU) and macroadenoma on imaging. Pre-operatively the patient was rendered euthyroid with carbimazole and underwent successful transphenoidal adenomectomy (TSA) with surgical cure. Histopathology displayed an elevated Ki-67 of 5.2%, necessitating long-term follow-up.

Learning points:

  • Thyrotropinomas are rare and likely under-diagnosed due to under-recognition of secondary hyperthyroidism.

  • Thyrotropinomas and other plurihormonal pit-1-derived adenomas are more aggressive adenomas according to WHO guidelines.

  • Co-secretion occurs in 30% of thyrotropinomas, requiring diligent investigation and long-term follow-up of complications.

Taxonomy:
Clinical Overview, Gland/Organ, Pituitary, Topic, Pituitary, Hormone, GH, IGF1, Prolactin, Thyroxine (T4), Triiodothyronine (T3), TSH, Condition/ Syndrome, Acromegaly, Goitre (multinodular), Hyperthyroidism, Hypogonadism, Pituitary adenoma, Plurihormonal pituitary adenoma, Thyrotrophic adenoma, Patient Demographics, Age, Adult, Gender, Male, Ethnicity, White, Country of Treatment, Australia, Diagnosis and Treatment, Signs and Symptoms, Anxiety, Dizziness, Goitre, Headache, Heat intolerance, Hypertension, Hyperthyroidism, Hypogonadism, Insomnia, Osteopenia, Palpitations, Tachycardia, Ventricular hypertrophy, Investigation, Angiography, Blood pressure, BMI, Bone mineral density, DEXA scan, Echocardiogram, FT3, FT4, GH, GH suppression, Haematoxylin and eosin staining, Heart rate, Histopathology, IGF1, Immunostaining, MRI, Pituitary function, Sex hormone binding globulin, SHBG, Thyroid function, Thyroid ultrasonography, TRH stimulation, Triiodothyronine (T3) suppression, TSH, Intervention, Resection of tumour, Transsphenoidal surgery, Medication, Aspirin, Beta-blockers, Carbimazole, Metoprolol, Statins, Related Disciplines, Surgery, Publication Details, Case Report Type, Unique/unexpected symptoms or presentations of a disease
DOI:
https://doi.org/10.1530/EDM-19-0068
Volume/Issue:
Volume 2019: Issue 1
Open access
Christine Yu Department of Medicine, University of California, Los Angeles, Los Angeles, California, 90095, USA

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Inder J Chopra Division of Endocrinology, Department of Medicine, University of California, 757 Westwood Plaza Blvd, Suite 7501, Los Angeles, CA, 90095, USA

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Edward Ha Department of Medicine, University of California, Los Angeles, Los Angeles, California, 90095, USA

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Summary

Ipilimumab, a novel therapy for metastatic melanoma, inhibits cytotoxic T-lymphocyte apoptosis, causing both antitumor activity and significant autoimmunity, including autoimmune thyroiditis. Steroids are frequently used in treatment of immune-related adverse events; however, a concern regarding the property of steroids to reduce therapeutic antitumor response exists. This study describes the first reported case of ipilimumab-associated thyroid storm and implicates iopanoic acid as an alternative therapy for immune-mediated adverse effects. An 88-year-old woman with metastatic melanoma presented with fatigue, anorexia, decreased functional status, and intermittent diarrhea for several months, shortly after initiation of ipilimumab – a recombinant human monoclonal antibody to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). On arrival, she was febrile, tachycardic, and hypertensive with a wide pulse pressure, yet non-toxic appearing. She had diffuse, non-tender thyromegaly. An electrocardiogram (EKG) revealed supraventricular tachycardia. Blood, urine, and stool cultures were collected, and empiric antibiotics were started. A computed tomography (CT) angiogram of the chest was negative for pulmonary embolism or pneumonia, but confirmed a diffusely enlarged thyroid gland, which prompted thyroid function testing. TSH was decreased at 0.16 μIU/ml (normal 0.3–4.7); free tri-iodothyronine (T3) was markedly elevated at 1031 pg/dl (normal 249–405), as was free thyroxine (T4) at 5.6 ng/dl (normal 0.8–1.6). With iopanoic acid and methimazole therapy, she markedly improved within 48 h, which could be attributed to lowering of serum T3 with iopanoic acid rather than to any effect of the methimazole. Ipilimumab is a cause of overt thyrotoxicosis and its immune-mediated adverse effects can be treated with iopanoic acid, a potent inhibitor of T4-to-T3 conversion.

Learning points

  • While ipilimumab more commonly causes autoimmune thyroiditis, it can also cause thyroid storm and clinicians should include thyroid storm in their differential diagnosis for patients who present with systemic inflammatory response syndrome.

  • Immune-related adverse reactions usually occur after 1–3 months of ipilimumab and baseline thyroid function testing should be completed before initiation with ipilimumab.

  • Conflicting data exist on the use of prednisone for treatment of CTLA4 adverse effects and its attenuation of ipilimumab's antitumor effect. Iopanoic acid may be considered as an alternative therapy in this setting.

Taxonomy:
Clinical Overview, Gland/Organ, Thyroid, Topic, Thyroid, Hormone, Thyroxine (T4), Triiodothyronine (T3), Condition/ Syndrome, Metastatic melanoma, Thyroid storm, Thyrotoxicosis, Patient Demographics, Age, Geriatric, Gender, Female, Ethnicity, White, Country of Treatment, United States, Diagnosis and Treatment, Signs and Symptoms, Abdominal pain, Anorexia, Anxiety, Atrial fibrillation, Chest pain, Diarrhoea, Fatigue, Goitre, Hypertension, Hyperthyroidism, Pyrexia, Tachycardia, Weight loss, Investigation, Angiography, Calcium (serum), CT scan, Electrocardiogram, FT3, FT4, Thyroid function, Total T3, Total T4, TSH, Ultrasound scan, Medication, Beta-blockers, Digoxin, Iopanoic acid, Ipilimumab, Methimazole, Metoprolol, Related Disciplines, Geriatrics, Oncology, Publication Details, Case Report Type, Unusual effects of medical treatment
DOI:
https://doi.org/10.1530/EDM-14-0092
Volume/Issue:
Volume 2015: Issue 1
Open access