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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

Huilin Koh, Manish Kaushik, Julian Kenrick Loh and Chiaw Ling Chng

Summary

Thyroid storm with multi-organ failure limits the use of conventional treatment. A 44-year-old male presented with thyroid storm and experienced cardiovascular collapse after beta-blocker administration, with resultant fulminant multi-organ failure requiring inotropic support, mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy. Hepatic and renal failure precluded the use of conventional thyroid storm treatment and early plasma exchange was instituted. The patient underwent emergency thyroidectomy after four effective exchanges, with subsequent rapid reversal of multi-organ failure. The challenges of institution of plasma exchanges with ongoing ECMO support, dialysis and timing of thyroidectomy are discussed. This case highlights the important role of early therapeutic plasma exchange (TPE) as an effective salvage therapy for lowering circulating hormones and stabilization of patients in preparation for emergency thyroidectomy in patients with thyroid storm and fulminant multi-organ failure.

Learning points:

  • Administration of beta-blockers in thyroid storm presenting with congestive cardiac failure may precipitate cardiovascular collapse due to inhibition of thyroid-induced hyperadrenergic compensation which maintains cardiac output.

  • TPE can be an effective bridging therapy to emergency total thyroidectomy when conventional thyroid storm treatment is contraindicated.

  • End-organ support using ECMO and CRRT can be combined with TPE effectively in the management of critically ill cases of thyroid storm.

  • The effectiveness of plasma exchange in lowering thyroid hormones appears to wane after 44–48 h of therapy in this case, highlighting the importance early thyroidectomy.

Open access

Jose León Mengíbar, Ismael Capel, Teresa Bonfill, Isabel Mazarico, Laia Casamitjana Espuña, Assumpta Caixàs and Mercedes Rigla

Summary

Durvalumab, a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules, is increasingly used in advanced neoplasias. Durvalumab use is associated with increased immune-related adverse events. We report a case of a 55-year-old man who presented to our emergency room with hyperglycaemia after receiving durvalumab for urothelial high-grade non-muscle-invasive bladder cancer. On presentation, he had polyuria, polyphagia, nausea and vomiting, and laboratory test revealed diabetic ketoacidosis (DKA). Other than durvalumab, no precipitating factors were identified. Pre-durvalumab blood glucose was normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. Simultaneously, he presented a thyroid hormone pattern that evolved in 10 weeks from subclinical hyperthyroidism (initially attributed to iodinated contrast used in a previous computerised tomography) to overt hyperthyroidism and then to severe primary hypothyroidism (TSH: 34.40 µU/mL, free thyroxine (FT4): <0.23 ng/dL and free tri-iodothyronine (FT3): 0.57 pg/mL). Replacement therapy with levothyroxine was initiated. Finally, he was tested positive for anti-glutamic acid decarboxylase (GAD65), anti-thyroglobulin (Tg) and antithyroid peroxidase (TPO) antibodies (Abs) and diagnosed with type 1 diabetes mellitus (DM) and silent thyroiditis caused by durvalumab. When durvalumab was stopped, he maintained the treatment of multiple daily insulin doses and levothyroxine. Clinicians need to be alerted about the development of endocrinopathies, such as DM, DKA and primary hypothyroidism in the patients receiving durvalumab.

Learning points:

  • Patients treated with anti-PD-L1 should be screened for the most common immune-related adverse events (irAEs).

  • Glucose levels and thyroid function should be monitored before and during the treatment.

  • Durvalumab is mainly associated with thyroid and endocrine pancreas dysfunction.

  • In the patients with significant autoimmune background, risk–benefit balance of antineoplastic immunotherapy should be accurately assessed.

Open access

Senhong Lee, Aparna Morgan, Sonali Shah and Peter R Ebeling

Summary

We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non–small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home. He subsequently has developed likely autoimmune thyroiditis and autoimmune encephalitis.

Learning points:

  • Glycemic surveillance in patients receiving immune checkpoint inhibitors is recommended.

  • Early glycemic surveillance after commencement of anti-programmed cell death-1 (PD-1) inhibitors may be indicated in selected populations, including patients with underlying type 2 diabetes mellitus and positive anti-glutamic acid decarboxylase (GAD) antibody.

  • Sodium-glucose co transporter-2 (SGLT2) inhibitors should be used with caution in patients on immunotherapy.

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

Eva Krčálová, Jiří Horáček, Lubomír Kudlej, Viera Rousková, Blanka Michlová, Irena Vyhnánková, Jiří Doležal, Jaroslav Malý and Pavel Žák

Summary

Radioiodine (RAI) has played a crucial role in differentiated thyroid cancer treatment for more than 60years. However, the use of RAI administration in patients with papillary thyroid microcarcinoma (even multifocal) is now being widely discussed and often not recommended. In accordance with European consensus, and contrary to the American Thyroid Association (ATA) guidelines, we recently performed RAI thyroid remnant ablation in a patient with differentiated papillary multifocal microcarcinoma. The post-therapeutic whole-body scan and SPECT/CT revealed the real and unexpected extent of disease, with metastases to upper mediastinal lymph nodes. This finding led to the patient’s upstaging from stage I to stage IVa according to the American Joint Committee on Cancer/International Union Against Cancer criteria.

Learning points

  • 131I is a combined beta–gamma emitter, thus allowing not only residual thyroid tissue ablation but also metastatic tissue imaging.

  • RAI remnant ablation omission also means post-treatment whole-body scan omission, which may lead to disease underestimation, due to incorrect nodal and metastatic staging.

  • RAI should be considered also in “low-risk” patients, especially when the lymph node involvement is not reliably documented.

  • Lower administered RAI activity (30mCi, 1.1GBq) may be a workable compromise in low-risk patients, not indicated for RAI remnant ablation according to ATA guidelines.

Open access

T Min, S Benjamin and L Cozma

Summary

Thyroid storm is a rare but potentially life-threatening complication of hyperthyroidism. Early recognition and prompt treatment are essential. Atrial fibrillation can occur in up to 40% of patients with thyroid storm. Studies have shown that hyperthyroidism increases the risk of thromboembolic events. There is no consensus with regard to the initiation of anticoagulation for atrial fibrillation in severe thyrotoxicosis. Anticoagulation is not routinely initiated if the risk is low on a CHADS2 score; however, this should be considered in patients with thyroid storm or severe thyrotoxicosis with impending storm irrespective of the CHADS2 risk, as it appears to increase the risk of thromboembolic episodes. Herein, we describe a case of thyroid storm complicated by massive pulmonary embolism.

Learning points

  • Diagnosis of thyroid storm is based on clinical findings. Early recognition and prompt treatment could lead to a favourable outcome.

  • Hypercoagulable state is a recognised complication of thyrotoxicosis.

  • Atrial fibrillation is strongly associated with hyperthyroidism and thyroid storm.

  • Anticoagulation should be considered for patients with severe thyrotoxicosis and atrial fibrillation irrespective of the CHADS2 score.

  • Patients with severe thyrotoxicosis and clinical evidence of thrombosis should be immediately anticoagulated until hyperthyroidism is under control.