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Open access

Thyrotropinoma with silent somatotroph and lactotroph adenoma during pregnancy

Yu-Fang Wu, Hui Yi Ng, Divya Namboodiri, David Lewis, Andrew Davidson, Bernard Champion, and Veronica Preda

Summary

Thyrotropinomas are an uncommon cause of hyperthyroidism and are exceedingly rarely identified during pregnancy, with limited evidence to guide management. Most commonly they present as macroadenomas and may cause symptoms of mass effect including headache, visual field defects and hypopituitarism. We present a case of a 35-year-old woman investigated for headaches in whom a 13 mm thyrotropinoma was found. In the lead-up to planned trans-sphenoidal surgery (TSS), she spontaneously conceived and surgery was deferred, as was pharmacotherapy, at her request. The patient was closely monitored through her pregnancy by a multi-disciplinary team and delivered without complication. Pituitary surgery was performed 6 months post-partum. Isolated secondary hypothyroidism was diagnosed postoperatively and replacement thyroxine was commenced. Histopathology showed a double lesion with predominant pituitary transcription factor-1 positive, steroidogenic factor negative plurihormonal adenoma and co-existent mixed thyroid-stimulating hormone, growth hormone, lactotroph and follicle-stimulating hormone staining with a Ki-67 of 1%. This case demonstrates a conservative approach to thyrotropinoma in pregnancy with a successful outcome. This highlights the need to consider the timing of intervention with careful consideration of risks to mother and fetus.

Learning points

  • Thyrotropinomas are a rare cause of secondary hyperthyroidism. Patients may present with hyperthyroidism or symptoms of mass effect, including headaches or visual disturbance.

  • Thyrotropinoma in pregnancy presents a number of pituitary-related risks including pituitary apoplexy and compression of local structures.

  • Hyperthyroidism in pregnancy raises the risk of complications including spontaneous abortion, preeclampsia, low birthweight and premature labour.

  • Timing of medical and surgical therapies must be carefully considered. A conservative approach requires careful monitoring in case emergent intervention is required.

Open access

A case series and literature review of necrobiosis lipoidica

Matthew J Verheyden, Natassia Rodrigo, Anthony J Gill, and Sarah J Glastras

Summary

Necrobiosis lipoidica (NL) is a rare and chronic disease characterised by yellow-brown, atrophic, telangiectatic plaques usually located on the lower extremities, with pathological features of collagen necrobiosis and dermal inflammation. Most cases are seen in those with diabetes mellitus, particularly type 1 diabetes (T1DM), and many without diabetes have evidence of abnormal glucose tolerance or family history of autoimmune disease. In this study, we describe four patients with NL and T1DM. A common theme is late identification and delay in diagnosis. Hence, we discuss the clinical features, need for clinicopathological correlation, and the management and prognostic implications for this distinctive entity. While most remain relatively asymptomatic, others progress to debilitating disease with pruritus, dysesthesia, and pain. Pain is often intense in the presence of ulcerated plaques, a morbid complication of NL. Diagnosis requires the integration of both clinical and histopathological findings. NL has proven a challenging condition to treat, and despite the numerous therapeutic modalities available, there is no standard of care. Hence, in this study, we provide an overview of current management strategies available for NL.

Learning points

  • Necrobiosis lipoidica (NL) is classically seen in patients with type 1 diabetes.

  • Koebner phenomenon, defined as the appearance of new skin lesions on previously unaffected skin secondary to trauma, is a well-recognised feature in NL.

  • Background skin phototype contributes to variable yellow appearance of lesions in NL.

  • Diagnosis of NL requires careful clinicopathological correlation.

  • NL is a chronic disease often refractory to treatment leading to significant morbidity for the patient and a management conundrum for the multidisciplinary healthcare team.

  • No standard therapeutic regimen has been established for the management of NL.

Open access

Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia

Adam I Kaplan, Catherine Luxford, and Roderick J Clifton-Bligh

Summary

Biallelic pathological variants in the thyroid stimulating hormone (TSH) subunit β gene (TSHB) result in isolated TSH deficiency and secondary hypothyroidism, a rare form of central congenital hypothyroidism (CCH), with an estimated incidence of 1 in 65 000 births. It is characterised by low levels of free thyroxine and inappropriately low serum TSH and may therefore be missed on routine neonatal screening for hypothyroidism, which relies on elevated TSH. We describe a patient with CCH who developed recurrence of pituitary hyperplasia and symptomatic hypothyroidism due to poor compliance with thyroxine replacement. She was diagnosed with CCH as a neonate and had previously required trans-sphenoidal hypophysectomy surgery for pituitary hyperplasia associated with threatened chiasmal compression at 17 years of age due to variable adherence to thyroxine replacement. Genetic testing of TSHB identified compound heterozygosity with novel variant c.217A>C, p.(Thr73Pro), and a previously reported variant c.373delT, p.(Cys125Valfs*10). Continued variable adherence to treatment as an adult resulted in recurrence of significant pituitary hyperplasia, which subsequently resolved with improved compliance without the need for additional medications or repeat surgery. This case describes a novel TSHB variant associated with CCH and demonstrates the importance of consistent compliance with thyroxine replacement to treat hypothyroidism and prevent pituitary hyperplasia in central hypothyroidism.

Learning points

  • Pathogenic variants in the TSH subunit β gene (TSHB) are rare causes of central congenital hypothyroidism (CCH).

  • c.217A>C, p.(Thr73Pro), is a novel TSHB variant, presented in association with CCH in this case report.

  • Thyroxine replacement is critical to prevent clinical hypothyroidism and pituitary hyperplasia.

  • Pituitary hyperplasia can recur post-surgery if adherence to thyroxine replacement is not maintained.

  • Pituitary hyperplasia can dramatically reverse if compliance with thyroxine replacement is improved to maintain free thyroxine (FT4) levels in the middle-to-upper normal range, without the need for additional medications or surgeries.

Open access

Acanthosis nigricans in a patient with metastatic insulinoma post peptide receptor radionuclide therapy

Jenny S W Yun, Chris McCormack, Michelle Goh, and Cherie Chiang

Summary

Acanthosis nigricans (AN) is a common dermatosis associated with hyperinsulinemia and insulin resistance. However, AN has been rarely reported in patients with insulinoma, a state of persistent hyperinsulinemia. We present a case of metastatic insulinoma, in whom AN manifested after the first cycle of peptide receptor radionuclide therapy (PRRT). A 40-year-old man was diagnosed with metastatic insulinoma after 5 months of symptomatic hypoglycemia. Within 1 month post PRRT, the patient became euglycemic but developed a pigmented, pruritic rash which was confirmed on biopsy as AN. We discuss the rare manifestation of AN in subjects with insulinoma, the role of insulin in the pathogenesis of AN, malignant AN in non-insulin-secreting malignancies and association with other insulin-resistant endocrinopathies such as acromegaly.

Learning points

  • Acanthosis nigricans (AN) is a common dermatosis which is typically asymptomatic and associated with the hyperinsulinemic state.

  • Malignant AN can rapidly spread, cause pruritus and affect mucosa and the oral cavity.

  • AN is extremely rare in patients with insulinoma despite marked hyperinsulinemia.

  • Peptide receptor radionuclide therapy might have triggered TGF-α secretion in this subject which led to malignant AN.

  • Rapid spread or unusual distribution of pruritic AN warrants further investigation to exclude underlying malignancy.

Open access

Accidental exposure to glimepiride from adulterated medication resulting in severe hypoglycaemia

Annabelle G Hayes, Mahesh M Umapathysivam, and David J Torpy

Summary

Sulphonylureas are insulinotropic and are not only useful in patients with diabetes but also act in non-diabetic individuals where hypoglycaemia and hyperinsulinism mimic insulinoma. We present a 63-year-old man who presented with inadvertent sulphonylurea-induced life-threatening hypoglycaemia on two occasions, resulting in hazardous and invasive investigation. Biochemistry revealed endogenous hyperinsulinaemia, with elevated serum c-peptide and insulin concentrations during symptomatic hypoglycaemia, and plasma glucose of 1.7 mmol/L. There was no history of sulphonylurea use prompting anatomical insulinoma studies to locate an insulinoma. However, a routine plasma insulinoma screen-detected glimepiride. Directed history implicated a medication taken for erectile dysfunction prior to disturbed consciousness, with alcohol. The tablets, obtained online, were analysed by mass spectrometry and contained tadalafil and dapoxetine as advertised but also contained glimepiride.

Learning points

  • Symptomatic unexplained hypoglycaemia requires investigation with plasma glucose level, c-peptide, insulin level, pro-insulin, beta-hydroxybutyrate, and a sulphonylurea screen regardless of known exposure to sulphonylureas.

  • Consider contamination of alternative or undisclosed medication, including PDE-5 inhibitor erectile dysfunction drugs.

  • Concomitant alcohol may impair glycogenolysis and gluconeogenesis, exacerbating hypoglycaemia.

Open access

Adrenal gland haemorrhages following motor vehicle accident with resultant adrenal insufficiency

Naomi Szwarcbard, Anna Davis, Leon A Bach, and Kathryn Hackman

Summary

Adrenal gland haemorrhage is an uncommon, yet likely under-diagnosed complication of high-impact trauma, such as motor vehicle accidents (MVA). It usually occurs with multi-trauma and is associated with additional injuries to the ribs, liver, kidney, spleen and vertebrae. Trauma cases with resultant adrenal gland injury have higher mortality rates. Primary adrenal insufficiency as a result of bilateral adrenal haemorrhage is potentially fatal. We report three cases of life-threatening adrenal insufficiency following adrenal injuries sustained in MVA’s. Case 1 was a 60-year-old-male who presented with acute haemodynamic instability on admission. Case 2 was an 88-year-old female on anticoagulation for atrial fibrillation, who developed haemodynamic instability 10 days into her admission. Case 3 was a 46-year-old male who developed hyponatraemia 2 weeks post-MVA. All were commenced on stress dose hydrocortisone replacement with improvement in clinical status. Only case 1 has had complete adrenal axis recovery, whereas the other patients remain on maintenance hydrocortisone replacement. Our cases demonstrate acute and subacute presentations of adrenal insufficiency following traumatic bilateral adrenal haemorrhages and highlight the importance of assessing adrenal morphology and function in any trauma patient with haemodynamic instability or hyponatraemia.

Learning points

  • Adrenal gland haemorrhage is an under-diagnosed consequence of high-impact trauma.

  • Trauma patients with adrenal haemorrhage have a significantly increased mortality risk.

  • Bilateral adrenal gland haemorrhage can result in life-threatening adrenal insufficiency requiring urgent glucocorticoid replacement.

  • Biochemical assessment of the adrenocortical axis should be considered in all patients presenting with high-impact trauma following motor vehicle accidents.

  • Given the potential for delayed presentation, any patients with new haemodynamic instability should have repeat biochemistry and/or imaging performed, even if initial adrenal imaging and investigations were normal.

Open access

Adrenal haemorrhage and infarction in the setting of vaccine-induced immune thrombocytopenia and thrombosis after SARS-CoV-2 (Oxford–AstraZeneca) vaccination

Anneke Graf, Eleni Armeni, Louise Dickinson, Matthew Stubbs, Brian Craven, Umasuthan Srirangalingam, and Teng-Teng Chung

Summary

Rare cases of vaccine-induced Immune thrombocytopenia and thrombosis (VITT) are being identified after vaccination with the SARS-CoV-2 Oxford–AstraZeneca vaccination. We report on two such patients with associated adrenal involvement, which is now being recognised. Both patients presented with abdominal pain, back pain and vomiting. Case 1 was a 46-year-old male who had received the first dose of the Oxford–AstraZeneca vaccination 8 days earlier. Imaging demonstrated a number of serious thrombotic complications including evolving bilateral adrenal haemorrhage (right adrenal haemorrhage identified at presentation, with the left-sided changes only evident on day 4 of the admission). Case 2 was a 38-year-old female who had received the first dose of Oxford–AstraZeneca vaccination 11 days prior. Imaging demonstrated left renal vein thrombosis and left adrenal infarction. VITT was diagnosed in both cases given these changes and other consistent haematological findings. Both patients were treated empirically for adrenal insufficiency, a diagnosis subsequently confirmed in case 1. We report these two cases of VITT presenting with adrenal complications (haemorrhage and infarction) after Oxford–AstraZeneca vaccination to highlight the association and the need for prompt management of co-existing adrenal insufficiency, especially given the potential for evolving adrenal involvement.

Learning points

  • Adrenal complications (thrombosis/infarction/haemorrhage) may develop as a part of vaccine-induced immune thrombocytopenia (VITT) after SARS-CoV-2 Oxford–AstraZeneca vaccination.

  • Evolving adrenal involvement is possible and ongoing assessment is required to identify this promptly.

  • Cortisol levels may be difficult to interpret when assessing for adrenal insufficiency, given high doses of corticosteroids may be used to manage VITT.

  • Clinicians should have a low threshold for starting empirical replacement with corticosteroids until reliable assessment of adrenal function can be performed.

Open access

Thyrotoxic periodic paralysis associated with Graves’ disease: a case series

S Ludgate, M Lin, M Mayadunne, J Steen, and K W Ho

Summary

Thyrotoxic periodic paralysis (TPP) is a rare condition characterised by acute onset hypokalaemia and paralysis which most commonly affects men of Asian descent between the ages of 20 and 40 years (, ). It has been reported in approximately 2% of patients with thyrotoxicosis in China and Japan (, , ). Hypokalaemia in TPP results from a massive intracellular shift of potassium induced by the thyroid hormone sensitisation of Na+/K+-ATPase (). Treatment of TPP includes prevention of this shift by using beta-blockade, rapid potassium replacement and treatment of the underlying hyperthyroidism. We present two cases of TPP with differing outcomes. In the first case, a 33-year-old Filipino gentleman presented to our emergency department (ED) with a 3-month history of recurrent proximal lower limb weakness. Serum potassium was 2.2 mmol/L (3.3–5.1) and he was given i.v. potassium replacement. Thyroid function tests (TFTs) and thyroid antibodies were consistent with Graves thyrotoxicosis. He was discharged home on carbimazole and remains well controlled on long-term medical therapy. In the second case, a 22-year-old Malaysian gentleman presented to our ED with new-onset bilateral lower limb painless paralysis. Serum potassium was 1.9 mmol/L with TFTs demonstrating Graves thyrotoxicosis. He was treated with i.v. potassium replacement and discharged home on carbimazole and propranolol. He represented to the hospital on two further occasions with TPP and was advised to consider total thyroidectomy given his refractory Graves’ disease. These cases highlight the importance of prompt recognition of this rare life-threatening complication of Graves’ disease, especially in patients of Asian descent.

Learning points

  • Thyrotoxic periodic paralysis is a rare condition characterised by hypokalaemia and acute painless muscle weakness in the presence of thyrotoxicosis.

  • The signs and symptoms of thyrotoxicosis can be subtle in these patients.

  • It is most commonly seen in Asian males between the ages of 20 and 40 and is most frequently caused by Graves’ disease.

  • Prompt recognition is essential as it is a life-threatening condition.

  • Urgent i.v. potassium replacement and beta-blockade with a non-selective beta-blocker are the mainstays of treatment.

  • i.v. potassium replacement should not be given in dextrose as this can potentiate hypokalaemia.

Open access

Monogenic diabetes due to an INSR mutation in a child with severe insulin resistance

Elaine E Sanderson, Mark Shah, Amanda J Hooper, Damon A Bell, and Catherine S Choong

Summary

We report a case of an 11-year-old girl presenting with a new diagnosis of diabetes associated with a heterozygous missense mutation in the insulin receptor (INSR) gene. This case highlights that INSR gene variants can be a cause for monogenic diabetes in children and adolescents and the need for genetic evaluation in atypical presentations of diabetes. We also describe the possible role of metformin in treating individuals with type A insulin resistance syndrome due to INSR gene variants.

Learning points

  • Insulin receptor (INSR) gene variants can be a cause of monogenic diabetes in children and adolescents.

  • Genetic evaluation should be considered in children and adolescents with type 2 diabetes (T2D), particularly where there is an atypical presentation and/or positive family history.

  • Metformin may have a role in the treatment of type A insulin resistance syndrome due to heterozygous mutation of the INSR gene.

Open access

Pitfalls and progress in adrenocortical carcinoma diagnosis: the utility of a multidisciplinary approach, immunohistochemistry and genomics

Ray Wang, Benjamin Solomon, Stephen J Luen, Owen W.J. Prall, Christine Khoo, Anthony J Gill, Jeremy Lewin, and Nirupa Sachithanandan

Summary

Adrenocortical carcinoma is a rare disease with poor prognosis whose clinical heterogeneity can at times present a challenge to accurate and timely diagnosis. We present the case of a patient who presented with extensive pulmonary lesions, mediastinal and hilar lymphadenopathy and an adrenal mass in whom the oncological diagnosis was initially uncertain. Through the use of immunohistochemistry, biochemistry and genomic testing, an accurate diagnosis of adrenocortical carcinoma was ultimately made which resulted in more directed treatment being administered. The use of multidisciplinary input and genomics to aid in diagnosis and prognosis of adrenocortical carcinoma is discussed.

Learning points

  • Adrenocortical carcinomas can present a diagnostic challenge to clinicians given it is a rare malignancy with significant clinical heterogeneity.

  • Specialist multidisciplinary team input is vital in the diagnosis and management of adrenocortical carcinomas.

  • Hormonal testing is recommended in the diagnostic workup of adrenal masses, even in the absence of overt clinical signs/symptoms of hormone excess.

  • Immunostaining for the highly sensitive and specific steroidogenic factor-1 is vital for accurate diagnosis.

  • Genomics can provide prognostic utility in management of adrenocortical carcinoma.