Farhana SharifDepartment of Paediatrics, Regional Hospital Mullingar, Co. Westmeath, Ireland Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland School of Medicine, University College Dublin, Dublin, Ireland
Graham Robert LeeSchool of Medicine, University College Dublin, Dublin, Ireland Department of Clinical Biochemistry and Diagnostic Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland
Rare patients who have both thyroid-stimulating hormone (TSH) receptor-stimulating and -blocking antibodies can develop ‘pendulum swinging’ thyroid dysfunction. A 9-year-old girl with Down syndrome was treated with carbimazole for Graves’ disease. After 2 years of treatment, she became profoundly biochemically hypothyroid, and this persisted after carbimazole was discontinued. Low-dose L-thyroxine was commenced. This was subsequently also discontinued as biochemical hyperthyroidism developed. TSH receptor antibody bioassay identified both TSH receptor-stimulating and -blocking antibodies. Mild hyperthyroidism persisted and while consultations regarding definitive treatment were ongoing, medication was not recommenced. Thyroid function normalised spontaneously and she has remained euthyroid for the past 3 years. Previous reports have advised definitive treatment; however, our patient developed spontaneous remission which has been prolonged and definitive therapies have been avoided. It is not yet known how commonly this particular phenomenon occurs.
Rare patients who have both TSH receptor-stimulating and -blocking antibodies can switch between hyperthyroidism and hypothyroidism or vice versa during treatment with antithyroid drugs or thyroxine.
Metamorphic thyroid autoimmunity is more common in Down syndrome.
Switching between hyperthyroidism and hypothyroidism and back again is less commonly reported.
Definitive treatment such as radioactive iodine or thyroidectomy are usually recommended.
Prolonged remission was achieved off all medication, without recourse to definitive treatments.
A patient treated with intramuscular testosterone replacement therapy for primary hypogonadism developed blurred vision shortly after receiving his testosterone injection. The symptom resolved over subsequent weeks and recurred after his next injection. A diagnosis of central serous chorioretinopathy (CSR) was confirmed following ophthalmology review. A decision was made to change the patient’s testosterone regime from this 12-weekly intramuscular injection to a daily topical testosterone gel, given the possibility that peak blood levels of testosterone following intramuscular injection were causing his ocular complaint. His CSR did not recur after this change in treatment. CSR secondary to testosterone therapy is a rare finding but has been reported previously in the literature.
Blurred vision in patients treated with testosterone replacement therapy (TRT) should prompt an ophthalmology review.
The potential for reduced risk of central serous chorioretinopathy (CSR) with daily transdermal testosterone remains a matter of conjecture.
Phaeochromocytoma, a rare neuroendocrine tumour of chromaffin cell origin, is characterised by catecholamine excess. Clinical presentation ranges from asymptomatic disease to life-threatening multiorgan dysfunction. Catecholamine-induced cardiomyopathy is a dreaded complication with high lethality. While there is lack of evidence-based guidelines for use of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) in the management of this condition, limited to case reports and small case series, V-A ECMO has been reported as ‘bridge to recovery’ therapy, providing circulatory support in the initial period of stabilisation prior to surgery. We report on two patients presenting with catecholamine-induced cardiomyopathy and circulatory collapse who were successfully treated with V-A ECMO for 5 and 6 days, respectively, providing initial haemodynamic support. After stabilisation and introduction of alpha-blockade, both cases had favourable outcomes, with successful laparoscopic adrenalectomies on days 62 and 83 of admission, respectively. Our case reports provide further support for the use of V-A ECMO in the treatment of such gravely ill patients.
Phaeochromocytoma should be considered in the diagnosis of patients presenting with acute cardiomyopathy.
Management of catecholamine-induced cardiomyopathy is complex and requires multidisciplinary specialist input.
Pre-operative management of phaeochromocytoma involves alpha-blockade; however, haemodynamic instability in the setting of cardiogenic shock can preclude alpha-blockade use.
Veno-arterial extracorporeal membrane oxygenation is a life-saving intervention which may be considered in cases of acute catecholamine-induced cardiomyopathy and cardiogenic shock in order to provide the required haemodynamic support in the initial phase of treatment, enabling the administration of traditional pharmacological agents, including alpha-blockade.
A 77-year-old female patient with a history of treated breast cancer and a recently diagnosed laryngeal cancer presented with severe hypercalcaemia associated with suppressed parathyroid hormone (PTH) levels. Her initial investigations included 25-hydroxy vitamin D levels, short synacthen test, bone scan, myeloma screen and thyroid function tests which were within normality. A computerised tomography (CT) scan showed some right lung apical fibrotic changes. Her PTH-related peptide (PTHrP) was normal and sarcoidosis was also excluded. Her previous and current malignancies were thought to be unlikely behind her hypercalcaemia. Her 1,25-dihydroxy vitamin D (calcitriol) levels were found to be elevated. Her hypercalcaemia was initially managed with intravenous fluids and intermittent bisphosphonates infusions which would transiently reduce her calcium levels. Steroid treatment was initiated which improved her hypercalcaemia; however, the calcium levels rebounded on tapering the steroids down, a pre-requisite prior to a positron emission computerised tomography (PET-CT) scan to determine the source of the excess calcitriol production. This was cancelled following an emergency admission with marked hypercalcaemia and acute renal and liver injury. A contemporary CT scan showed a right apical lung mass with hepatic lesions suggestive of a disseminated lung primary. The histology obtained from a liver biopsy was compatible with metastatic small-cell lung carcinoma. Unfortunately, her clinical condition deteriorated further and she did not survive. To the best of our knowledge, this is the first report in the literature describing calcitriol-mediated hypercalcaemia due to a small-cell lung cancer.
Paraneoplastic hypercalcaemia may manifest even without overt detection of the primary cancer.
The workup for paraneoplastic hypercalcaemia should be meticulous.
Both bisphosphonates and steroids are useful in the initial management of calcitriol-mediated hypercalcaemia, but the definitive management is the treatment of the cause.
Insulinomas are rare pancreatic neuroendocrine neoplasms (NENs) that are typically sporadic and solitary, with the majority being <2 cm in diameter at diagnosis. The median duration of symptoms before diagnosis is variable; however, this is usually in the region of 12–18 months. We report on an insulinoma diagnosed some 25 years following initial symptoms, having by that stage attained a diameter of 4 cm. We present a 50-year-old man who was reported with hypoglycaemic symptoms on his wedding 25 years prior to eventual confirmation of an insulinoma. He had since learned to live with the symptoms by eating frequently to manage his hypoglycaemia. However, over recent months, he reported a substantial deterioration in his symptoms, and indeed, had collapsed on two occasions. He had a fasting glucose of 2.9 mmol/L with grossly inappropriate elevated insulin and C-peptide levels. MRI demonstrated a 4.1 cm lesion at the body of pancreas and an indeterminate 9-mm liver lesion with a negative 68Gallium-DOTATATE PET scan. Accordingly, he was initiated on diazoxide and referred to the surgical team for distal pancreatectomy: histology confirmed a 4.4-cm well-differentiated pancreatic NEN of intermediate grade (NEN G2, Grade 2, 2017 World Health Organization (WHO) pancreatic-NEN classification), with positive immunohistochemistry for insulin. His hypoglycaemia episodes have ceased, and he remains under active surveillance. Our case demonstrates the possibility of dietary control of insulinoma-induced hypoglycaemia, and the likelihood that such a prolonged delay in diagnosis has led to the uncommonly large size of the apparently benign tumour which is usually ‘small and indolent’.
Most patients with insulinomas have lesions that are 1–2 cm in size, with 96% being less than 3 cm.
The mean tumour size of insulinomas found in 3 of the largest reported series was 1.5 cm, with a range of 0.1–7.0 cm.
It is not uncommon for patients to have symptoms for several months to years before diagnosis; however, no reported cases had the symptoms such long for 25 years, and the large size of the tumour in this case may reflect the very long history.
Subacute thyroiditis is an inflammatory disorder of the thyroid gland that has previously been described following viral illnesses and occasionally post vaccination such as influenza vaccine. 2021 was a revolutionary year for the development of SARS-CoV-2 vaccinations with multiple different vaccines now available. There are increasing numbers of case reports of thyroiditis following these vaccinations. We report a case of a 50-year-old female who developed subacute thyroiditis 6 days post ChAdOx1 nCoV-19 vaccine (AZD1222 produced by AstraZeneca Vaxzevria). The initial thyrotoxic phase was followed by overt hypothyroidism. This resolved spontaneously within 5 months without levothyroxine replacement. We hope that our case will add to the growing literature of cases of thyroiditis occurring after multiple different types of SARS-CoV-2 vaccination and create awareness of this rare but treatable adverse effect. We also review the literature on the proposed mechanisms behind this adverse effect.
Subacute thyroiditis is an inflammatory disorder of the thyroid gland that can occur after a viral illness or vaccination against certain infections.
Subacute thyroiditis is a rare adverse effect that has been reported to occur after different types of SARS-CoV-2 vaccinations.
Subacute thyroiditis post vaccination is relatively straightforward to manage, with some patients requiring non-steroidal anti-inflammatory drugs and beta-blockers, while more severe cases may require corticosteroid therapy. This adverse effect should not dissuade vaccination use at a population level.
There are many postulated mechanisms for the development of subacute thyroiditis following vaccination including the presence of the ACE-2 receptor for SARS-CoV-2 on the thyroid gland, an inflammatory/immune response as is seen in COVID-19 infection itself and molecular mimicry between SARS-CoV-2 spike protein and healthy thyroid antigen.
Vasoactive intestinal peptide-secreting tumours (VIPomas) are an extremely rare form of functional pancreatic neuroendocrine tumour with an estimated annual incidence of 1 in 10 million. Associated tumour hypersecretion of other peptides, including pancreatic polypeptide (PPomas), may also be seen. These malignancies classically present with a defined triad of refractory diarrhoea, hypokalaemia and metabolic acidosis known as Verner–Morrison syndrome. Diagnosis is frequently delayed, and the majority of patients will have metastatic disease at presentation. Symptoms are usually well controlled with somatostatin analogue administration. Here we report a case of metastatic mixed VIPoma/PPoma-induced diarrhoea causing renal failure so severe that ultrafiltration was required to recover adequate renal function.
Profuse, watery diarrhoea is a common presenting complaint with a multitude of aetiologies. This, combined with the rarity of these tumours, makes diagnosis difficult and frequently delayed. A functional neuroendocrine tumour should be suspected when diarrhoea is unusually extreme, prolonged and common causes have been promptly excluded.
These patients are likely to be profoundly unwell on presentation. They are extremely hypovolaemic with dangerous electrolyte and metabolic abnormalities. Aggressive initial rehydration and electrolyte replacement are imperative. A somatostatin analogue should be commenced as soon as the diagnosis is suspected.
This is an extreme example of Verner–Morrison syndrome. We are unaware of another case where renal failure secondary to diarrhoea and dehydration was so severe that renal replacement therapy was required to restore adequate renal function, further emphasising how critically unwell these patients can be.
Both the primary tumour and metastases showed a remarkably good and rapid response to somatostatin analogue administration. Cystic change and involution were noted on repeat imaging within days.
Prior to his illness, this patient was extremely high functioning with no medical history. His diagnosis was an enormous psychological shock, and the consideration and care for his psychological well-being were a crucial part of his overall management. It highlights the importance of a holistic approach to cancer care and the role of the clinical nurse specialist within the cancer multidisciplinary team.
The coexistence of autoimmune diabetes and maturity-onset diabetes (MODY) is rare. The absence of pancreatic autoantibodies is a key factor prompting MODY genetic testing. In this study, we report three cases of young-onset diabetes with progressive beta-cell dysfunction, strongly positive glutamic acid decarboxylase (GAD) antibodies, and genetic confirmation of pathogenic gene variants of HNF-1A, HNF-4A, and ABCC8-MODY. The first case is a woman diagnosed with HNF-1A-MODY diabetes more than 30 years after her diagnosis of adult-onset diabetes at 25 years. She required insulin after her fourth pregnancy. She became ketotic on oral hypoglycaemic agents (OHAs) and subsequently, her GAD antibodies tested positive. The second case is a woman diagnosed with diabetes at 17 years who was subsequently diagnosed with HNF-4A-MODY after many hypoglycaemic episodes on low-dose insulin. GAD antibodies were strongly positive. The last case is a man diagnosed with diabetes at 26 years who was well controlled on OHAs and required insulin years later due to sudden deterioration in glycaemic control. His ABCC8-MODY was diagnosed upon realisation of strong family history and his GAD antibodies tested positive. All subjects are now treated with insulin. Less than 1% of subjects with MODY have positive autoantibodies. These cases highlight individuals who may have two different types of diabetes simultaneously or consecutively. Deterioration of glycaemic control in subjects with MODY diabetes should highlight the need to look for the emergence of autoantibodies. At each clinic visit, one should update the family history as MODY was diagnosed in each case after the development of diabetes in their offspring.
These cases highlight the rare coexistence of autoimmune diabetes and MODY.
Deterioration of glycaemic control in subjects with MODY diabetes should highlight the emergence of autoantibodies.
One should revise and update the family history as the diagnosis of MODY was made after the development of diabetes in offspring.
Understanding the spectrum of diabetes allows for precision medicine.
COVID-19 is associated with severe disease in pregnancy. Complications of the disease, or simultaneous diagnoses, may be missed if clinicians do not retain a large differential diagnosis when assessing such women. Starvation ketoacidosis is one such diagnosis which may complicate the disease and should not be missed. A 37-year-old woman, 33 weeks’ gestation presented with breathlessness. Clinical history, examination and investigations supported a diagnosis of starvation ketosis of pregnancy complicating COVID-19 pneumonitis. Prompt correction of the metabolic disturbance resulted in resolution, and preterm delivery was avoided at this time. Early recognition and prompt management of starvation ketosis of pregnancy in women with COVID-19 are important in reducing maternal and neonatal morbidity and mortality. Preterm delivery may be avoided with prompt resolution of the metabolic disturbance. Clinicians should keep a wide differential diagnosis when assessing women with breathlessness. A multidisciplinary team (MDT) approach is required to facilitate optimal care.
Clinicians should maintain a wide differential when assessing women who are unwell with COVID-19 in pregnancy.
Complications such as starvation ketoacidosis are rare but life-threatening.
An awareness of such complications facilitates early identification of the condition, and involvement of appropriate specialists who can initiate optimal and timely management.
In the context of pregnancy, where ketoacidosis poses a threat to the mother or baby, prompt management and resolution may avoid preterm delivery.
Conditions that may increase the risk of developing starvation ketoacidosis include pregnancy, medication use such as corticosteroids or tocolytic therapies, previous gastric surgery, intercurrent illness and pregnancy-related conditions that might contribute towards a degree of chronic starvation.
Multidisciplinary input supports the delivery of best practice and care for the patients.
A 53-year-old female presented to a tertiary ophthalmology referral centre complaining of unilateral painless loss of vision. Subsequent assessment revealed malignant hypertension causing right-sided cystoid macular oedema. During the course of secondary hypertension workup, she was diagnosed with a 7.8 cm phaeochromocytoma which was resected. Testing for a panel of all predisposing phaeochromocytoma-causing variants using next-generation sequencing resulted in the diagnosis of a novel SDHD variant.
Screening for secondary causes of hypertension is indicated when there is evidence of hypertension-mediated end-organ damage ().
Testing for a predisposing variant should be considered in all patients with phaeochromocytoma or paraganglioma due to the high heritability rate and prevalence of somatic variants (, , ).
Novel variants are commonly uncovered in the Succinate Dehydrogenase (SDH) subunit; proving pathogenicity is a complex, time-consuming process and one challenge of next-generation sequencing ().
SDHB immunohistochemistry as a tool for demonstrating pathogenicity is associated with reduced sensitivity when assessing SDHD variants (, ).