J K Witczak, N Ubaysekara, R Ravindran, S Rice, Z Yousef and L D Premawardhana
Maria Tomkins, Roxana Maria Tudor, Diarmuid Smith and Amar Agha
This case is the first to describe a patient who experienced concomitant agranulocytosis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis as an adverse effect of propylthiouracil treatment for Graves’ disease. A 42-year-old female with Graves’ disease presented to the emergency department (ED) with a 2-week history of fevers, night sweats, transient lower limb rash, arthralgia, myalgia and fatigue. She had been taking propylthiouracil for 18 months prior to presentation. On admission, agranulocytosis was evident with a neutrophil count of 0.36 × 109/L and immediately propylthiouracil was stopped. There was no evidence of active infection and the patient was treated with broad-spectrum antibodies and one dose of granulocyte colony-stimulation factor, resulting in a satisfactory response. On further investigation, ANCAs were positive with dual positivity for proteinase 3 and myeloperoxidase. There was no evidence of end-organ damage secondary to vasculitis, and the patient’s constitutional symptoms resolved completely on discontinuation of the drug precluding the need for immunosuppressive therapy.
- Continued vigilance and patient education regarding the risk of antithyroid drug-induced agranulocytosis is vital throughout the course of treatment.
- ANCA-associated vasculitis is a rare adverse effect of antithyroid drug use.
- Timely discontinuation of the offending drug is vital in reducing end-organ damage and the need for immunosuppressive therapy in drug-induced ANCA-associated vasculitis.
- Similarities in the pathogenesis of agranulocytosis and drug-induced ANCA-associated vasculitis may offer insight into an improved understanding of vasculitis and agranulocytosis.
Carolina Shalini Singarayar, Foo Siew Hui, Nicholas Cheong and Goay Swee En
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.
- 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.
Tessa Glyn, Beverley Harris and Kate Allen
We present the case of a 57-year-old lady who had a delayed diagnosis of central hypothyroidism on a background of Grave’s thyrotoxicosis and a partial thyroidectomy. During the twenty years following her partial thyroidectomy, the patient developed a constellation of symptoms and new diagnoses, which were investigated by numerous specialists from various fields, namely rheumatology, renal and respiratory. She developed significantly impaired renal function and raised creatine kinase (CK). She was also referred to a tertiary neurology service for investigation of myositis, which resulted in inconclusive muscle biopsies. Recurrently normal TSH results reassured clinicians that this did not relate to previous thyroid dysfunction. In 2015, she developed increased shortness of breath and was found to have a significant pericardial effusion. The clinical biochemist reviewed this lady’s blood results and elected to add on a free T4 (fT4) and free T3 (fT3), which were found to be <0.4 pmol/L (normal range (NR): 12–22 pmol/L) and 0.3 pmol/L (NR: 3.1–6.8 pmol/L), respectively. She was referred urgently to the endocrine services and commenced on Levothyroxine replacement for profound central hypothyroidism. Her other pituitary hormones and MRI were normal. In the following year, her eGFR and CK normalised, and her myositis symptoms, breathlessness and pericardial effusion resolved. One year following initiation of Levothyroxine, her fT4 and fT3 were in the normal range for the first time. This case highlights the pitfalls of relying purely on TSH for excluding hypothyroidism and the devastating effect the delay in diagnosis had upon this patient.
- Isolated central hypothyroidism is very rare, but should be considered irrespective of previous thyroid disorders.
- If clinicians have a strong suspicion that a patient may have hypothyroidism despite normal TSH, they should ensure they measure fT3 and fT4.
- Laboratories that do not perform fT3 and fT4 routinely should review advice sent to requesting clinicians to include a statement explaining that a normal TSH excludes primary but not secondary hypothyroidism.
- Thyroid function tests should be performed routinely in patients presenting with renal impairment or a raised CK.
V Larouche and M Tamilia
Enteroviruses, including coxsackieviruses and Echovirus, are well known pathogens responsible for the development of thyroiditis. We describe the case of a 49-year-old woman with no personal or family history of thyroid disease who presented to the emergency room with a two-week history of daily fevers up to 39°C, a sore throat, occasional palpitations and diaphoresis, decreased appetite and an unintentional 10 kg weight loss over the same time course Physical examination revealed mild tachycardia, an intention tremor and a normal-sized, nontender thyroid gland without palpable nodules. The remainder of the physical examination was unremarkable and without stigmata of Graves’ disease. Her initial blood tests revealed overt thyrotoxicosis, elevated liver enzymes, an elevated C-reactive protein, a negative monospot and a positive CMV IgM antibody. Thyroid sonography revealed areas of hypoechogenicity and relatively low vascularity. Fine-needle biopsy showed a lymphocytic infiltrate. The patient was treated symptomatically with propranolol. On follow-up, the patient became euthyroid, and her liver enzymes normalised. Previous cases of CMV-induced thyroiditis occurred in immunosuppressed patients. This is the first reported case of a CMV-mononucleosis-induced thyroiditis in an immunocompetent adult patient and serves as a reminder that viral illnesses are a common cause of thyroiditis with abnormal liver enzymes.
- The differential diagnosis of thyrotoxicosis with abnormal liver enzymes includes severe hyperthyroidism and thyroid storm caused by Graves’ disease as well as the thyrotoxic phase of a thyroiditis, usually caused by a virus such as coxsackievirus or, in this case, cytomegalovirus.
- Cytomegalovirus appears to be a recently recognized causal agent for thyroiditis, both in immunosuppressed and immunocompetent patients.
- Careful follow-up of thyroid function tests in patients with thyroiditis allows clinicians to determine if patients’ thyroid hormone secretion normalizes or if they remain hypothyroid.
Wei Lin Tay, Wann Jia Loh, Lianne Ai Ling Lee and Chiaw Ling Chng
We report a patient with Graves’ disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves’ ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion.
- It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.
- TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves’ ophthalmopathy.
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.
- 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.
R D’Arcy, M McDonnell, K Spence and C H Courtney
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.
- 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.
Alfredo Di Cerbo, Federica Pezzuto and Alessandro Di Cerbo
Graves’ disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves’ disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves’ disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves’ disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves’ disease and synergize the stimulatory activity of Graves’ IgGs.
- Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.
- The coexistence of acromegaly and Graves’ disease is a very unusual event, the prevalence being <1%.
- Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade.
- We report the first case of a severe form of Graves’ disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves’ disease.
Catarina Roque, Ricardo Fonseca, Carlos Tavares Bello, Carlos Vasconcelos, António Galzerano and Sância Ramos
Primary adrenal lymphoma is a rare malignancy. It frequently presents bilaterally and with symptoms of adrenal insufficiency. Amiodarone may induce secondary organ dysfunction, and thyrotoxicosis develops in 15% of cases. The symptomatology of both conditions is nonspecific, especially in the elderly, and a high suspicion index is necessary for appropriate diagnosis. A 78-year-old female presented to the emergency department with confusion, nausea and vomiting. She had recently been to the emergency department with urinary tract infection, vomiting and acute hypochloremic hyponatremia. Upon re-evaluation, the leukocyturia persisted and because of TSH 0.01 µU/mL and free-T4 68 (10–18) pmol/L, she was admitted to the Endocrinology ward. Further evaluation supported amiodarone-induced thyroiditis type 2. Sepsis ensued, in the setting of nosocomial pneumonia. Hemodynamic instability, hyponatremia, hypoglycemia and vomiting raised the suspicion of adrenocortical insufficiency. Fluid resuscitation and hydrocortisone led to clinical improvement, and adrenal insufficiency was admitted. The thoracoabdominal tomography suggested an endobronchic primary lesion with hepatic and adrenal secondary deposits (6.6 and 7 cm), but this was confirmed neither on pleural effusion nor on bronchofibroscopic fluid analyses. The adrenals were not accessible for biopsy. Despite high-dose hydrocortisone maintenance, the patient died before definite diagnosis. The autopsy confirmed primary non-Hodgkin lymphoma.
- Primary adrenal lymphoma is a rare cause of adrenal insufficiency, but progression can be fast and fatal.
- Hyperpigmentation is frequently absent.
- The presenting symptoms are nonspecific and might mimic infection. Disproportion of the general state with signs of specific organ symptomatology is a diagnostic clue.
- Infection may precipitate adrenal crisis and worsen thyroid function with further adrenal insufficiency exacerbation.
- In the context of thyrotoxicosis, there may be little clinical response to a therapeutic trial with standard dose glucocorticoids.
- High-dose glucocorticoid substitution may be required to achieve clinical stability in thyrotoxic patients.