, insomnia and a degree of weight loss. There was no clear precipitant to the symptoms reported and no suggestion of recent infection. On clinical examination he appeared tremulous and diaphoretic. There was a regular tachycardia of 110 bpm, and mild
R D’Arcy, M McDonnell, K Spence and C H Courtney
Jonathan Brown and Luqman Sardar
A 68-year-old previously independent woman presented multiple times to hospital over the course of 3 months with a history of intermittent weakness, vacant episodes, word finding difficulty and reduced cognition. She was initially diagnosed with a TIA, and later with a traumatic subarachnoid haemorrhage following a fall; however, despite resolution of the haemorrhage, symptoms were ongoing and continued to worsen. Confusion screen blood tests showed no cause for the ongoing symptoms. More specialised investigations, such as brain imaging, cerebrospinal fluid analysis, electroencephalogram and serology also gave no clear diagnosis. The patient had a background of hypothyroidism, with plasma thyroid function tests throughout showing normal free thyroxine and a mildly raised thyroid-stimulating hormone (TSH). However plasma anti-thyroid peroxidise (TPO) antibody titres were very high. After discussion with specialists, it was felt she may have a rare and poorly understood condition known as Hashimoto’s encephalopathy (HE). After a trial with steroids, her symptoms dramatically improved and she was able to live independently again, something which would have been impossible at presentation.
- In cases of subacute onset confusion where most other diagnoses have already been excluded, testing for anti-thyroid antibodies can identify patients potentially suffering from HE.
- In these patients, and under the guidance of specialists, a trial of steroids can dramatically improve patient’s symptoms.
- The majority of patients are euthyroid at the time of presentation, and so normal thyroid function tests should not prevent anti-thyroid antibodies being tested for.
- Due to high titres of anti-thyroid antibodies being found in a small percentage of the healthy population, HE should be treated as a diagnosis of exclusion, particularly as treatment with steroids may potentially worsen the outcome in other causes of confusion, such as infection.
I R Wallace, E Healy, R S Cooke, P K Ellis, R Harper and S J Hunter
TSH-secreting pituitary adenomas are rare and the optimal investigation and management is uncertain. We describe a case of a 43 year-old woman with a TSH-secreting pituitary adenoma, highlighting diagnostic testing and our use, pre-operatively of somatostatin analogue therapy, which induced biochemical euthyroidism and a reduction in tumour size.
- The differential diagnosis of the syndrome of inappropriate TSH secretion is non-thyroidal illness, medications, assay interference due to heterophilic antibodies, thyroid hormone resistance and TSH-secreting pituitary adenoma.
- TRH stimulation test and triiodothyronine suppression test assist in differentiating thyroid hormone resistance and TSH-secreting pituitary adenoma.
- Somatostatin analogue therapy can induce biochemical euthyroidism and reduce tumour size.
Motoyuki Igata, Kaku Tsuruzoe, Junji Kawashima, Daisuke Kukidome, Tatsuya Kondo, Hiroyuki Motoshima, Seiya Shimoda, Noboru Furukawa, Takeshi Nishikawa, Nobuhiro Miyamura and Eiichi Araki
Resistance to thyroid hormone (RTH) is a syndrome of reduced tissue responsiveness to thyroid hormones. RTH is majorly caused by mutations in the thyroid hormone receptor beta (THRB) gene. Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear. Here, we report a rare case of RTH with a papillary thyroid carcinoma (PTC). A 26-year-old woman was referred to our hospital due to a thyroid tumor and hormonal abnormality. She had elevated serum thyroid hormones and non-suppressed TSH levels. Genetic analysis of THRB identified a missense mutation, P452L, leading to a diagnosis of RTH. Ultrasound-guided fine-needle aspiration biopsy of the tumor and lymph nodes enabled the cytological diagnosis of PTC with lymph node metastases. Total thyroidectomy and neck lymph nodes dissection were performed. Following surgery, thyroxine replacement (≥500 μg) was necessary to avoid the symptoms of hypothyroidism and to maintain her TSH levels within the same range as before the operation. During the follow-up, basal thyroglobulin (Tg) levels were around 6 ng/ml and TSH-stimulated Tg levels were between 12 and 20 ng/ml. Up to present, the patient has had no recurrence of PTC. This indicates that these Tg values are consistent with a biochemical incomplete response or an indeterminate response. There is no consensus regarding the management of thyroid carcinoma in patients with RTH, but aggressive treatments such as total thyroidectomy followed by radioiodine (RAI) and TSH suppression therapy are recommended.
- There are only a few cases reporting the coexistence of RTH and thyroid carcinoma. Moreover, our case would be the first case presenting one with lymph node metastases.
- Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear.
- When total thyroidectomy is performed in patients with RTH, a large amount of thyroxine is needed to maintain their thyroid function.
- There is no consensus regarding the management of thyroid carcinoma in patient with RTH, but effective treatments such as total thyroidectomy followed by RAI and TSH suppression therapy are recommended.
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.
Arshiya Tabasum, Ishrat Khan, Peter Taylor, Gautam Das and Onyebuchi E Okosieme
TSH receptor antibodies (TRAbs) are the pathological hallmark of Graves’ disease, present in nearly all patients with the disease. Euthyroid Graves’ ophthalmopathy (EGO) is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves’ ophthalmopathy (GO) was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves’ disease.
- Euthyroid Graves’ ophthalmopathy can present initially with negative thyroid-specific autoantibodies.
- Patients with suggestive symptoms of ophthalmopathy should be carefully evaluated for GO with imaging studies even when thyroid function and autoantibodies are normal.
- Patients with EGO can develop thyroid dysfunction within 4 years of follow-up underpinning the need for long-term follow-up and continued patient and physician vigilance in patients who have been treated for EGO.
Elizabeth M Madill, Shamil D Cooray and Leon A Bach
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.
- Thyroiditis as a complication of parathyroidectomy surgery is uncommon but represents an under-recognised phenomenon.
- It is thought to occur due to mechanical damage of thyroid follicles by vigorous palpation.
- Palpation of the thyroid gland may impair the physical integrity of the follicular basement membrane, with consequent development of an inflammatory response.
- The majority of patients are asymptomatic, however clinically significant thyrotoxicosis occurs in a minority.
- Patients should be advised of thyroiditis/thyrotoxicosis as a potential complication of the procedure.
- Testing of thyroid function should be performed if clinically indicated, particularly if adrenergic symptoms occur post-operatively with no other cause identified.
Sarah Y Qian, Matthew J L Hare, Alan Pham and Duncan J Topliss
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.
- Hypoglycaemia is defined by Whipple’s triad and can be provoked by fasting or mixed-meal tests.
- Although uncommon, insulinomas can present with post-prandial hypoglycaemia.
- 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.
- Improved imaging techniques including MRI, endoscopic ultrasound and functional nuclear medicine scans aid localisation of insulinomas.
- Despite advances in imaging and surgical techniques, accurate resection of insulinomas remains challenging.
Ehtasham Ahmad, Kashif Hafeez, Muhammad Fahad Arshad, Jimboy Isuga and Apostolos Vrettos
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.
- Occurrence of Graves’ disease after primary hypothyroidism is uncommon but possible.
- In this case, there was a time-lapse of almost 28 years and therefore this entity may not be as rare as previously thought.
- Diagnosis requires careful clinical and biochemical assessment. Otherwise, the case can be easily confused for over-replacement of levothyroxine.
- We suggest measuring both anti-thyroid peroxidase (TPO) antibodies and TSH receptor antibodies (TRAB) in suspected cases.
- The underlying aetiology for the conversion is not exactly known but probably involves autoimmune switch by an external stimulus in genetically susceptible individuals.
Xin Chen, Dina Kamel, Braden Barnett, Evan Yung, Adrienne Quinn and Caroline Nguyen
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.
- There has been an increasing awareness of post gastric bypass hypoglycemia (PGBH).
- Histopathologically, PGBH can vary from minimal changes to nesidioblastosis.
- Although uncommon, patients with PGBH after Roux-en-Y gastric bypass may present with both postprandial and fasting hyperinsulinemic hypoglycemia as disease progresses.
- Our hypothesis for this phenomenon is that the insulin release becomes dissociated from food stimulation and is increased at baseline with disease progression.