Diagnosis and Treatment > Signs and Symptoms
Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Heath Park, Cardiff, UK
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Summary
Graves’ disease is associated with tachydysrythmia, cardiac ischaemia and cardiomyopathy – all uncommon in young adults without previous cardiac disease. We present three young individuals who developed cardiac complications after periods of uncontrolled Graves’ disease. Subject 1: A 34-year-old female had severe thyrotoxic symptoms for weeks. Investigations showed fT4: 98.4 (11–25 pmol/L), fT3: 46.9 (3.1–6.8 pmol/L), TSH <0.01 (0.27–4.2 mU/L) and thyrotrophin receptor antibody (TRAb): 34.8 (<0.9 U//l). She had appropriate treatment but several weeks later she became breathless despite improving thyroid function. Echocardiography showed a pericardial effusion of 2.9 cm. She responded well to steroids and NSAIDs but developed active severe Graves’ orbitopathy after early total thyroidectomy. Subject 2: A 28-year-old male developed thyrotoxic symptoms (fT4: 38 pmol/L, fT3: 13.9 pmol/L, TSH <0.01 (for over 6 months) and TRAb: 9.3 U/L). One month after starting carbimazole, he developed acute heart failure (HF) due to severe dilated cardiomyopathy – EF 10–15%. He partially recovered after treatment – EF 28% and had early radioiodine treatment. Subject 3: A 42-year-old woman who had been thyrotoxic for several months (fT4: 54.3; fT3 >46.1; TSH <0.01; TRAb: 4.5) developed atrial fibrillation (AF) and heart failure. Echocardiography showed cardiomegaly – EF 29%. She maintains sinus rhythm following early total thyroidectomy (EF 50%). Significant cardiac complications may occur in previously fit young adults, who have had uncontrolled Graves’ disease for weeks to months. Cardiac function recovers in the majority, but early definitive treatment should be discussed to avoid Graves’ disease relapse and further cardiac decompensation.
Learning points:
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Cardiac complications of Graves’ disease are uncommon in young adults without previous cardiac disease.
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These complications may however occur if Graves’ disease had been poorly controlled for several weeks or months prior to presentation.
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Persistent symptoms after adequate control should alert clinicians to the possibility of cardiac disease.
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Specific treatment of Graves’ disease and appropriate cardiac intervention results in complete recovery in the majority and carries a good prognosis.
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Early definitive treatment should be offered to them to prevent cardiac decompensation at times of further relapse.
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Summary
There has been an increasing awareness of post gastric bypass hypoglycemia (PGBH). Histopathologic findings from such patients who underwent partial/total pancreatomy, however, can vary widely from minimal changes to classic nesidioblastosis, making the pathologic diagnosis challenging. PGBH typically presents as postprandial hypoglycemia, as opposed to insulinoma, which presents as fasting hypoglycemia. Herein, we describe an unusual case of a patient with PGBH who initially presented with postprandial hypoglycemia three years after surgery, but later developed fasting hyperinsulinemic hypoglycemia as the disease progressed. Our hypothesis for this phenomenon is that this disease is progressive, and later in its course, the insulin release becomes dissociated from food stimulation and is increased at baseline. Future studies are needed to investigate the prevalence as well as etiology of this progression from postprandial to fasting hypoglycemia.
Learning points:
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There has been an increasing awareness of post gastric bypass hypoglycemia (PGBH).
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Histopathologically, PGBH can vary from minimal changes to nesidioblastosis.
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Although uncommon, patients with PGBH after Roux-en-Y gastric bypass may present with both postprandial and fasting hyperinsulinemic hypoglycemia as disease progresses.
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Our hypothesis for this phenomenon is that the insulin release becomes dissociated from food stimulation and is increased at baseline with disease progression.
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Summary
Primary hypothyroidism is a common endocrine condition, most commonly caused by autoimmune thyroiditis (Hashimoto’s disease) while Graves’ disease is the most common cause of hyperthyroidism. Hypothyroidism is usually a permanent condition in most patients requiring lifelong levothyroxine treatment. Transformation from Hashimoto’s disease to Graves’ disease is considered rare but recently been increasingly recognised. We describe a case of a 61-year-old lady who was diagnosed with hypothyroidism approximately three decades ago and treated with levothyroxine replacement therapy. Approximately 27 years after the initial diagnosis of hypothyroidism, she started to become biochemically and clinically hyperthyroid. This was initially managed with gradual reduction in the dose of levothyroxine, followed by complete cessation of the medication, but she remained hyperthyroid, ultimately requiring anti-thyroid treatment with Carbimazole. This case highlights that there should be a high index of suspicion for a possible conversion of hypothyroidism to hyperthyroidism, even many years after the initial diagnosis of hypothyroidism. To our knowledge, this case illustrates the longest reported time interval between the diagnosis of hypothyroidism until the conversion to hyperthyroidism.
Learning points:
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Occurrence of Graves’ disease after primary hypothyroidism is uncommon but possible.
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In this case, there was a time-lapse of almost 28 years and therefore this entity may not be as rare as previously thought.
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Diagnosis requires careful clinical and biochemical assessment. Otherwise, the case can be easily confused for over-replacement of levothyroxine.
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We suggest measuring both anti-thyroid peroxidase (TPO) antibodies and TSH receptor antibodies (TRAB) in suspected cases.
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The underlying aetiology for the conversion is not exactly known but probably involves autoimmune switch by an external stimulus in genetically susceptible individuals.
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Department of Medicine, Monash University, Melbourne, Australia
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Summary
Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (68Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas. The lesion was excised and histopathology was confirmed a localised well-differentiated neuroendocrine pancreatic neoplasm. There have been no significant episodes of hypoglycaemia since. This case highlights several key points. Insulinoma should be sought in proven post-prandial hyperinsulinaemic hypoglycaemia – even in the absence of fasting hypoglycaemia. The use of nuclear imaging targeting somatostatin and GLP1 receptors has improved accuracy of localisation. Despite these advances, accurate surgical resection can remain challenging.
Learning points:
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Hypoglycaemia is defined by Whipple’s triad and can be provoked by fasting or mixed-meal tests.
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Although uncommon, insulinomas can present with post-prandial hypoglycaemia.
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In hypoglycaemia following gastrointestinal surgery (i.e. bariatric surgery or less commonly Nissen fundoplication) dumping syndrome or non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) should be considered.
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Improved imaging techniques including MRI, endoscopic ultrasound and functional nuclear medicine scans aid localisation of insulinomas.
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Despite advances in imaging and surgical techniques, accurate resection of insulinomas remains challenging.
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
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Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
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Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
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Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
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Summary
Bariatric surgery is an effective therapy for obesity but is associated with long-term complications such as dumping syndromes and nutritional deficiencies. We report a case of a 26-year-old caucasian female, with history of morbid obesity and gestational diabetes (GDM), who became pregnant 4 months after Roux-en-Y bypass surgery. She developed GDM during subsequent pregnancy, which was initially managed with metformin and insulin. Nocturnal hypoglycaemia causing sleep disturbance and daytime somnolence occured at 19 weeks of pregnancy (19/40). Treatment with rapid-acting carbohydrates precipitated further hypoglycaemia. Laboratory investigations confirmed hypoglycaemia at 2.2 mmol/L with appropriately low insulin and C-peptide, intact HPA axis and negative IgG insulin antibodies. The patient was seen regularly by the bariatric dietetic team but concerns about compliance persisted. A FreeStyle Libre system was used from 21/40 enabling the patient a real-time feedback of changes in interstitial glucose following high or low GI index food intake. The patient declined a trial of acarbose but consented to an intraveneous dextrose infusion overnight resulting in improvement but not complete abolishment of nocturnal hypoglycaemia. Hypoglycaemias subsided at 34/40 and metformin and insulin had to be re-introduced due to high post-prandial blood glucose readings. An emergency C-section was indicated at 35 + 1/40 and a small-for-gestational-age female was delivered. There have been no further episodes of hypoglycaemia following delivery. This case illustrates challenges in the management of pregnancy following bariatric surgery. To our knowledge, this is the first use of FreeStyle Libre in dumping syndrome in pregnancy following bariatric surgery with troublesome nocturnal hypoglycaemia.
Learning points:
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Bariatric surgery represents the most effective treatment modality in cases of severe obesity. With increasing prevalence of obesity, more people are likely to undergo bariatric procedures, many of which are women of childbearing age.
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Fertility generally improves after bariatric surgery due to weight reduction, but pregnancy is not recommended for at least 12–24 months after surgery. If pregnancy occurs, there are currently little evidence-based guidelines available on how to manage complications such as dumping syndromes or gestational diabetes (GDM) in women with history of bariatric surgery.
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Diagnosis of GDM relies on the use of a 75 g oral glucose tolerance test (OGTT). The use of this test in pregnant women is not recommended due to its potential to precipitate dumping syndrome. Capillary glucose monitoring profiles or continuous glucose monitoring (CGM) is being currently discussed as alternative testing modalities.
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As the CGM technology becomes more available, including the recently introduced FreeStyle Libre Flash glucose monitoring system, more pregnant women, including those after bariatric surgery, will have access to this technology. We suggest urgent development of guidelines regarding the use of CGM and flash glucose monitoring tools in these circumstances and in the interim recommend careful consideration of their use on a case-to-case basis.
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Summary
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.
Learning points:
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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.
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Cytomegalovirus appears to be a recently recognized causal agent for thyroiditis, both in immunosuppressed and immunocompetent patients.
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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.
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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:
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Free tri-iodothyronine (T3) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.
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Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.
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Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.
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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.
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Summary
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.
Learning points:
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Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.
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The coexistence of acromegaly and Graves’ disease is a very unusual event, the prevalence being <1%.
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Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade.
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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.
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Department of Medicine (Alfred), Monash University, Melbourne, Victoria, Australia
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Summary
Thyrotoxicosis is an under-recognised but clinically important complication of parathyroidectomy. We report a case of a 37-year-old man with tertiary hyperparathyroidism who initially developed unexplained anxiety, diaphoresis, tachycardia, tremor and hyperreflexia one day after subtotal parathyroidectomy. Thyroid biochemistry revealed suppressed thyroid stimulating hormone and elevated serum free T4 and free T3 levels. Technetium-99m scintigraphy scan confirmed diffusely decreased radiotracer uptake consistent with thyroiditis. The patient was diagnosed with thyrotoxicosis resulting from palpation thyroiditis. Administration of oral beta-adrenergic antagonists alleviated his symptoms and there was biochemical evidence of resolution fourteen days later. This case illustrates the need to counsel patients about thyroiditis as one of the potential risks of parathyroid surgery. It also emphasises the need for biochemical surveillance in patients with unexplained symptoms in the post-operative period and may help to minimise further invasive investigations for diagnostic clarification.
Learning points
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Thyroiditis as a complication of parathyroidectomy surgery is uncommon but represents an under-recognised phenomenon.
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It is thought to occur due to mechanical damage of thyroid follicles by vigorous palpation.
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Palpation of the thyroid gland may impair the physical integrity of the follicular basement membrane, with consequent development of an inflammatory response.
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The majority of patients are asymptomatic, however clinically significant thyrotoxicosis occurs in a minority.
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Patients should be advised of thyroiditis/thyrotoxicosis as a potential complication of the procedure.
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Testing of thyroid function should be performed if clinically indicated, particularly if adrenergic symptoms occur post-operatively with no other cause identified.
