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Open access

Hui Yi Ng, Divya Namboodiri, Diana Learoyd, Andrew Davidson, Bernard Champion and Veronica Preda

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.
Open access

Diana Oliveira, Mara Ventura, Miguel Melo, Sandra Paiva and Francisco Carrilho

Summary

Addison’s disease (AD) is the most common endocrine manifestation of antiphospholipid syndrome (APS), but it remains a very rare complication of the syndrome. It is caused by adrenal venous thrombosis and consequent hemorrhagic infarction or by spontaneous (without thrombosis) adrenal hemorrhage, usually occurring after surgery or anticoagulant therapy. We present a clinical case of a 36-year-old female patient with a previous diagnosis of APS. She presented with multiple thrombotic events, including spontaneous abortions. During evaluation by the third episode of abortion, a CT imaging revealed an adrenal hematoma, but the patient was discharged without further investigation. A few weeks later, she presented in the emergency department with manifestations suggestive of adrenal insufficiency. Based on that assumption, she started therapy with glucocorticoids, with significant clinical improvement. After stabilization, additional investigation confirmed AD and excluded other etiologies; she also started mineralocorticoid replacement. This case illustrates a rare complication of APS that, if misdiagnosed, may be life threatening. A high index of suspicion is necessary for its diagnosis, and prompt treatment is crucial to reduce the morbidity and mortality potentially associated.

Learning points:

  • AD is a rare but life-threatening complication of APS.
  • It is important to look for AD in patients with APS and a suggestive clinical scenario.
  • APS must be excluded in patients with primary adrenal insufficiency and adrenal imaging revealing thrombosis/hemorrhage.
  • Glucocorticoid therapy should be promptly initiated when AD is suspected.
  • Mineralocorticoid replacement must be started when there is confirmed aldosterone deficiency.
  • Hypertension is a common feature of APS; in patients with APS and AD, replacement therapy with glucocorticoids and mineralocorticoids may jeopardize hypertension management.
Open access

Carolina Shalini Singarayar, Foo Siew Hui, Nicholas Cheong and Goay Swee En

Summary

Thyrotoxicosis is associated with cardiac dysfunction; more commonly, left ventricular dysfunction. However, in recent years, there have been more cases reported on right ventricular dysfunction, often associated with pulmonary hypertension in patients with thyrotoxicosis. Three cases of thyrotoxicosis associated with right ventricular dysfunction were presented. A total of 25 other cases of thyrotoxicosis associated with right ventricular dysfunction published from 1994 to 2017 were reviewed along with the present 3 cases. The mean age was 45 years. Most (82%) of the cases were newly diagnosed thyrotoxicosis. There was a preponderance of female gender (71%) and Graves’ disease (86%) as the underlying aetiology. Common presenting features included dyspnoea, fatigue and ankle oedema. Atrial fibrillation was reported in 50% of the cases. The echocardiography for almost all cases revealed dilated right atrial and or ventricular chambers with elevated pulmonary artery pressure. The abnormal echocardiographic parameters were resolved in most cases after rendering the patients euthyroid. Right ventricular dysfunction and pulmonary hypertension are not well-recognized complications of thyrotoxicosis. They are life-threatening conditions that can be reversed with early recognition and treatment of thyrotoxicosis. Signs and symptoms of right ventricular dysfunction should be sought in all patients with newly diagnosed thyrotoxicosis, and prompt restoration of euthyroidism is warranted in affected patients before the development of overt right heart failure.

Learning points:

  • Thyrotoxicosis is associated with right ventricular dysfunction and pulmonary hypertension apart from left ventricular dysfunction described in typical thyrotoxic cardiomyopathy.
  • Symptoms and signs of right ventricular dysfunction and pulmonary hypertension should be sought in all patients with newly diagnosed thyrotoxicosis.
  • Thyrotoxicosis should be considered in all cases of right ventricular dysfunction or pulmonary hypertension not readily explained by other causes.
  • Prompt restoration of euthyroidism is warranted in patients with thyrotoxicosis complicated by right ventricular dysfunction with or without pulmonary hypertension to allow timely resolution of the abnormal cardiac parameters before development of overt right heart failure.
Open access

Mallika Bhat, Matty Mozzor, Savneek Chugh, Vamsi Buddharaju, Monica Schwarcz and Guy Valiquette

Summary

We describe detailed administration of thyroidal and extrathyroidal doses of radioiodine to a patient with end-stage renal disease on hemodialysis. A thorough description of area under curve measurements in a patient with compromised renal function has rarely been described in the literature. Few publications have described thyroid cancer management of patients on hemodialysis, and we believe our management will aid in patient treatment in the future.

Learning points:

  • Scheduling of hemodialysis is important when administering radioactive iodine.
  • Treatment of thyroid cancer with radioiodine in patients with end-stage renal disease requires multidisciplinary approach coordinating dialysis, nuclear medicine and endocrinologists care.
  • Balancing ideal dosage of I131 and the timing of dialysis to insure maximal thyroidal uptake and minimal extra thyroidal I131 concentration is necessary.
Open access

Carlos Tavares Bello, Emma van der Poest Clement and Richard Feelders

Summary

Cushing’s syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing’s syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing’s disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing’s syndrome.

Learning points:

  • Severe Cushing’s syndrome is not always caused by ectopic ACTH secretion.
  • Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.
  • Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.
  • Cushing’s syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.
  • Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing’s syndrome.
Open access

Colin L Knight, Shamil D Cooray, Jaideep Kulkarni, Michael Borschmann and Mark Kotowicz

A 51 year old man presented with sepsis in the setting of thioamide-induced agranulocytosis. Empiric broad-spectrum antibiotics was followed by directed narrow-spectrum antibiotics, and his neutrophil count recovered with support from granulocyte-colony stimulating factor (G-CSF) analogue transfusions. After a brief period of multi-modal therapy for nine days including potassium iodide (Lugol’s iodine), cholestyramine, propanolol and lithium to temper his persisting hyperthyroidism, a total thyroidectomy was performed while thyroid hormone levels remained at thyrotoxic levels. Postoperative recovery was uncomplicated and he was discharged home on thyroxine. There is limited available evidence to guide treatment in this unique cohort of patients who require prompt management to avert impending clinical deterioration. This case report summarises the successful emergent control of thyrotoxicosis in the setting of thioamide-induced agranulocytosis complicated by sepsis, and demonstrates the safe use of multi-modal pharmacological therapies in preparation for total thyroidectomy.

Learning points:

  • Thioamide-induced agranulocytosis is an uncommon but potentially life-threatening complication of which all prescribers and patients need to be aware.
  • A multi-modal preoperative pharmacological approach can be successful, even when thioamides are contraindicated, when needing to prepare a thyrotoxic patient for semi-urgent total thyroidectomy.
  • There is not enough evidence to confidently predict the safe timing when considering total thyroidectomy in this patient cohort, and therefore it should be undertaken when attempts have first been made to safely reduce thyroid hormone levels.
  • Thyroid storm is frequently cited as a potentially severe complication of thyroid surgery undertaken in thyrotoxic patients, although the evidence does not demonstrate this as a common occurrence.
Open access

R D’Arcy, M McDonnell, K Spence and C H Courtney

Summary

A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T4). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T3) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1–6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging (123I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement.

Learning points:

  • Free tri-iodothyronine (T3) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.
  • Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.
  • Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.
  • Medicines and supplements sourced online for weight loss may contain thyroxine (T4) or T3 and should be considered as a cause of unexplained exogenous hyperthyroidism.
Open access

Kazuyuki Oishi, Daisuke Takabatake and Yuichi Shibuya

Summary

We experienced a case of an 82-year-old woman who presented to our hospital with a 1-month history of dysphagia and dyspnea. Cervical contrast-enhanced computed tomography revealed diffuse thyroid neoplasms causing significant tracheal stenosis with tumors, particularly of the superior mediastinum, which were associated with an embolism of the brachiocephalic vein and suspected invasion to the bilateral common carotid arteries. Anaplastic thyroid cancer (ATC) was diagnosed by fine-needle aspiration; thus, emergency tracheostomy and gastrostomy were performed. We made a definitive diagnosis of ATC (T4bN0M0 Stage IVB) and initiated continuous lenvatinib administration at 24 mg/day. Although several adverse events occurred, the tumor size reduced remarkably over a short period. However, the patient died from rupture of the common carotid artery 30 days after treatment initiation. Here, we report our experience with lenvatinib therapy for ATC and include a literature review.

Learning points:

  • Lenvatinib is extremely effective for ATC.
  • Lenvatinib has a much greater cytoreductive effect than traditional therapies, but it needs dose reduction or withdrawal because of treatment-related side effects.
  • Lenvatinib may cause treatment-related carotid blowout syndrome, resulting in death for patients with invasion to the carotid artery.
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

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.