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Open access

Taisuke Uchida, Hideki Yamaguchi, Kazuhiro Nagamine, Tadato Yonekawa, Eriko Nakamura, Nobuhiro Shibata, Fumiaki Kawano, Yujiro Asada and Masamitsu Nakazato

Summary

We report a case of rapid pleural effusion after discontinuation of lenvatinib. A 73-year-old woman was diagnosed with poorly differentiated thyroid cancer with right pleural metastasis. Weekly paclitaxel treatment was performed for 18 weeks, but it was not effective. Oral administration of lenvatinib, a multi-target tyrosine kinase inhibitor, reduced the size of cervical and thoracic tumors and lowered serum thyroglobulin levels. Lenvatinib was discontinued on day 28 because of Grade 2 thrombocytopenia and Grade 3 petechiae. Seven days after discontinuation of lenvatinib, the patient was hospitalized because of dyspnea and right pleural effusion. Pleural effusion rapidly improved with drainage and re-initiation of lenvatinib and did not recur. Anorexia caused by lenvatinib led to undernutrition, which resulted in death 13 months after initiation of lenvatinib. Autopsy revealed extensive necrosis with primary and metastatic lesions, suggesting that the patient responded to lenvatinib. Physicians should be aware of the possibility of flare-up in patients with thyroid cancer treated with lenvatinib.

Learning points:

  • Autopsy findings revealed that lenvatinib was efficacious in treating poorly differentiated thyroid cancer without primary lesion resection.

  • Flare-up phenomenon may occur in thyroid cancer treated with lenvatinib.

  • Attention should be paid to flare-up phenomenon within a few days of discontinuing lenvatinib.

Open access

Su Ann Tee, Earn Hui Gan, Mohamad Zaher Kanaan, David Ashley Price, Tim Hoare and Simon H S Pearce

Summary

Primary adrenal insufficiency secondary to syphilis is extremely rare, with only five cases being reported in the literature. We report a case of adrenal insufficiency as a manifestation of Treponema pallidum infection (tertiary syphilis). A 69-year-old, previously fit and well Caucasian male was found to have adrenal insufficiency after being admitted with weight loss, anorexia and postural dizziness resulting in a fall. Biochemical testing showed hyponatraemia, hyperkalaemia, and an inadequate response to Synacthen testing, with a peak cortisol level of 302 nmol/L after administration of 250 µg Synacthen. Abdominal imaging revealed bilateral adrenal hyperplasia with inguinal and retroperitoneal lymphadenopathy. He was started on hydrocortisone replacement; however, it was not until he re-attended ophthalmology with a red eye and visual loss 1 month later, that further work-up revealed the diagnosis of tertiary syphilis. Following a course of penicillin, repeat imaging 5 months later showed resolution of the abnormal radiological appearances. However, adrenal function has not recovered and 3 years following initial presentation, the patient remains on both glucocorticoid and mineralocorticoid replacement. In conclusion, this case highlights the importance of considering syphilis as a potential differential diagnosis in patients presenting with adrenal insufficiency and bilateral adrenal masses, given the recent re-emergence of this condition. The relative ease of treating infectious causes of adrenal lesions makes accurate and timely diagnosis crucial.

Learning points:

  • Infectious causes, including syphilis, should be excluded before considering adrenalectomy or biopsy for any patient presenting with an adrenal mass.

  • It is important to perform a full infection screen including tests for human immunodeficiency virus, other blood-borne viruses and concurrent sexually transmitted diseases in patients presenting with bilateral adrenal hyperplasia with primary adrenal insufficiency.

  • Awareness of syphilis as a potential differential diagnosis is important, as it not only has a wide range of clinical presentations, but its prevalence has been increasing in recent times.

Open access

Carine Ghassan Richa, Khadija Jamal Saad, Georges Habib Halabi, Elie Mekhael Gharios, Fadi Louis Nasr and Marie Tanios Merheb

Summary

The objective of this study is to report three cases of paraneoplastic or ectopic Cushing syndrome, which is a rare phenomenon of the adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. Three cases are reported in respect of clinical presentation, diagnosis and treatment in addition to relevant literature review. The results showed that ectopic ACTH secretion can be associated with different types of neoplasm most common of which are bronchial carcinoid tumors, which are slow-growing, well-differentiated neoplasms with a favorable prognosis and small-cell lung cancer, which are poorly differentiated tumors with a poor outcome. The latter is present in two out of three cases and in the remaining one, primary tumor could not be localized, representing a small fraction of patients with paraneoplastic Cushing. Diagnosis is established in the setting of high clinical suspicion by documenting an elevated cortisol level, ACTH and doing dexamethasone suppression test. Treatment options include management of the primary tumor by surgery and chemotherapy and treating Cushing syndrome. Prognosis is poor in SCLC. We concluded that in front of a high clinical suspicion, ectopic Cushing syndrome diagnosis should be considered, and identification of the primary tumor is essential.

Learning points:

  • Learning how to suspect ectopic Cushing syndrome and confirm it among all the causes of excess cortisol.

  • Distinguish between occult and severe ectopic Cushing syndrome and etiology.

  • Providing the adequate treatment of the primary tumor as well as for the cortisol excess.

  • Prognosis depends on the differentiation and type of the primary malignancy.

Open access

Lourdes Balcázar-Hernández, Guadalupe Vargas-Ortega, Yelitza Valverde-García, Victoria Mendoza-Zubieta and Baldomero González-Virla

Summary

The craniopharyngiomas are solid cystic suprasellar tumors that can present extension to adjacent structures, conditioning pituitary and hypothalamic dysfunction. Within hypothalamic neuroendocrine dysfunction, we can find obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, imbalances in the regulation of body temperature, thirst, heart rate and/or blood pressure and alterations in dietary intake (like anorexia). We present a rare case of anorexia–cachexia syndrome like a manifestation of neuroendocrine dysfunction in a patient with a papillary craniopharyngioma. Anorexia–cachexia syndrome is a complex metabolic process associated with underlying illness and characterized by loss of muscle with or without loss of fat mass and can occur in a number of diseases like cancer neoplasm, non-cancer neoplasm, chronic disease or immunodeficiency states like HIV/AIDS. The role of cytokines and anorexigenic and orexigenic peptides are important in the etiology. The anorexia–cachexia syndrome is a clinical entity rarely described in the literature and it leads to important function limitation, comorbidities and worsening prognosis.

Learning points:

  • Suprasellar lesions can result in pituitary and hypothalamic dysfunction.

  • The hypothalamic neuroendocrine dysfunction is commonly related with obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, but rarely with anorexia–cachexia.

  • Anorexia–cachexia syndrome is a metabolic process associated with loss of muscle, with or without loss of fat mass, in a patient with neoplasm, chronic disease or immunodeficiency states.

  • Anorexia–cachexia syndrome results in important function limitation, comorbidities that influence negatively on treatment, progressive clinical deterioration and bad prognosis that can lead the patient to death.

  • Anorexia–cachexia syndrome should be suspected in patients with emaciation and hypothalamic lesions.

Open access

Andrea Pucci, Wui Hang Cheung, Jenny Jones, Sean Manning, Helen Kingett, Marco Adamo, Mohamed Elkalaawy, Andrew Jenkinson, Nicholas Finer, Jacqueline Doyle, Majid Hashemi and Rachel L Batterham

Summary

Sleeve gastrectomy (SG) is the second most commonly performed bariatric procedure worldwide. Altered circulating gut hormones have been suggested to contribute post-operatively to appetite suppression, decreased caloric intake and weight reduction. In the present study, we report a 22-year-old woman who underwent laparoscopic SG for obesity (BMI 46 kg/m2). Post-operatively, she reported marked appetite reduction, which resulted in excessive weight loss (1-year post-SG: BMI 22 kg/m2, weight loss 52%, >99th centile of 1-year percentage of weight loss from 453 SG patients). Gastrointestinal (GI) imaging, GI physiology/motility studies and endoscopy revealed no anatomical cause for her symptoms, and psychological assessments excluded an eating disorder. Despite nutritional supplements and anti-emetics, her weight loss continued (BMI 19 kg/m2), and she required nasogastric feeding. A random gut hormone assessment revealed high plasma peptide YY (PYY) levels. She underwent a 3 h meal study following an overnight fast to assess her subjective appetite and circulating gut hormone levels. Her fasted nausea scores were high, with low hunger, and these worsened with nutrient ingestion. Compared to ten other post-SG female patients, her fasted circulating PYY and nutrient-stimulated PYY and active glucagon-like peptide 1 (GLP1) levels were markedly elevated. Octreotide treatment was associated with suppressed circulating PYY and GLP1 levels, increased appetite, increased caloric intake and weight gain (BMI 22 kg/m2 after 6 months). The present case highlights the value of measuring gut hormones in patients following bariatric surgery who present with anorexia and excessive weight loss and suggests that octreotide treatment can produce symptomatic relief and weight regain in this setting.

Learning points

  • Roux-en-Y gastric bypass and SG produce marked sustained weight reduction. However, there is a marked individual variability in this reduction, and post-operative weight loss follows a normal distribution with extremes of ‘good’ and ‘poor’ response.

  • Profound anorexia and excessive weight loss post-SG may be associated with markedly elevated circulating fasted PYY and post-meal PYY and GLP1 levels.

  • Octreotide treatment can produce symptomatic relief and weight regain for post-SG patients that have an extreme anorectic and weight loss response.

  • The present case highlights the value of measuring circulating gut hormone levels in patients with post-operative anorexia and extreme weight loss.

Open access

Christine Yu, Inder J Chopra and Edward Ha

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.