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Krishna Prabha Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India

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K Felix Jebasingh Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India

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Vaibhav Londhe Department of Obstetrics and Gynaecology, Unit II, Christian Medical College and Hospital, Vellore, Tamil Nadu, India

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Nihal Thomas Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India

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Summary

Ovarian hyperstimulation syndrome (OHSS) usually occurs in patients undergoing assisted reproduction techniques and ovulation induction. Its variant, spontaneous ovarian hyperstimulation syndrome, a potentially life-threatening disorder, is uncommon and only a few cases have been reported in association with hypothyroidism. This study analysed five patients with untreated chronic hypothyroidism presenting with multicystic ovaries, isosexual precocious puberty, and delayed bone age; subsequently, the follow-up and regression of ovarian pathology was assessed. Two patients had presented to the emergency department with menorrhagia and hypotension, of these, one had ovarian torsion at presentation. Three patients presented to the outpatient department: one for evaluation of short stature, one for premature menarche, and another with polycystic ovaries. They were all diagnosed with long-standing, untreated chronic hypothyroidism. There was regression of the size of the cystic ovaries on subsequent follow-up. In all these patients, long-standing hypothyroidism had resulted in ovarian hyperstimulation syndrome. The potentially life-threatening complications of this syndrome may be prevented by careful screening and a strong index of clinical suspicion at the outset.

Learning points

  • Long-standing, untreated primary hypothyroidism may result in spontaneous ovarian hyperstimulation syndrome.

  • A high index of suspicion is required for an early and accurate diagnosis.

  • The requirement for interdepartmental collaboration between gynaecology and endocrinology departments is essential for the successful management of this life-threatening but easily treatable disorder.

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Junith Thomas Department of Transfusion Medicine, Jubilee Mission Medical College, Thrissur, Kerala, India

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Rohini Sebastian Department of Pathology, Jubilee Mission Medical College, Thrissur, Kerala, India

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C R Anil Kumar Department of General Medicine, Jubilee Mission Medical College, Thrissur, Kerala, India

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Aboobacker Mohamed Rafi Department of Transfusion Medicine, Jubilee Mission Medical College, Thrissur, Kerala, India

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Summary

Although most published cases of lead poisoning come from occupational exposures, some traditional remedies may also contain toxic amounts of lead. Here, we report the case of a 58-year-old female who presented with abdominal pain, generalized tiredness, and decreased food intake, with anemia and elevated levels of lead. The patient was found to be taking herbal capsules for diabetes prior to the presentation. This case highlights the need for increased awareness that some herbal remedies may contain potentially harmful levels of heavy metals, and people who use them are at risk of developing associated toxicities.

Learning points

  • Individuals who support traditional medicine often incorrectly believe that herbal remedies for diabetes are free from side effects, leading them to favor these treatments over contemporary medications.

  • Herbal medications are freely available online, even without a prescription.

  • The accessibility of herbal medicines without prescriptions, coupled with the false belief in their lack of side effects, misleads educated individuals toward quackery treatments. Misinformation spread via social media exacerbates this issue.

  • Heavy metals are present in toxic levels in the drugs, causing complications.

  • Lead is the most common heavy metal found in such herbal medicines.

  • Lead poisoning leads to anemia and other systemic complications which could have been fatal if not found in time.

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Presoon Kuruvilla Department of Internal Medicine, Caritas Hospital, Kerala, India

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Angel John Department of Internal Medicine, Caritas Hospital, Kerala, India

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Ashith Murali Department of Internal Medicine, Caritas Hospital, Kerala, India

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Summary

Insulin autoantibody syndrome (IAS) or Hirata’s disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes. Insulin autoantibodies are diagnostic for the condition. Hirata’s disease has been seen to be associated with other autoimmune conditions. Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology. Although autoimmunity plays a role in the pathogenesis of both the diseases, association between the two has not been reported till date. In our case, a 72-year-old Indian woman with vitiligo for the past 30 years presented with recurrent episodes of fasting hypoglycaemia. She was found to have very high levels of fasting insulin, C-peptide, and insulin antibody and was diagnosed with IAS. Thus, we conclude that the clinical spectrum of Hirata’s disease has to be taken as more heterogenous than previously assumed.

Learning points

  • Insulin autoantibody syndrome (IAS) or Hirata’s disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes in which insulin plays a major role.

  • Insulin autoantibodies are diagnostic for IAS. The endocrine insulin and its autoantibodies play a major role in the pathogenesis of the disease.

  • Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology.

  • IAS and vitiligo are two diseases with autoimmune aetiology which has been seen to be associated with each other (the first case to be reported).

  • The clinical spectrum of Hirata’s disease has to be taken as more heterogenous than previously assumed.

  • On dealing with autoimmune diseases, we should also keep in mind about other diseases with autoimmune pathogenesis.

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Aneez Joseph Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, India

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Kripa Elizabeth Cherian Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, India

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Nitin Kapoor Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, India

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Thomas V Paul Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, India

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Summary

Tenofovir-induced osteomalacia secondary to proximal renal tubular dysfunction is not an uncommon complication known to occur. A 46-year-old woman was referred for the evaluation of osteoporosis which was diagnosed elsewhere. She had polyarthralgia, bony pains and proximal muscle weakness of 1 year duration. She was diagnosed to have HIV infection and was on antiretroviral therapy that consisted of tenofovir, lamivudine and efavirenz for the past 12 years. She had attained menopause 5 years back. On examination, she had bone tenderness, proximal myopathy and painful restriction of movement of her lower limbs. Investigations showed features of renal tubular acidosis, hypophosphatemia and raised alkaline phosphatase that were suggestive of osteomalacia. X-ray of the pelvis showed diffuse osteopenia and an MRI of the pelvis done showed multiple insufficiency fractures involving the head of femur on both sides. Following this, her tenofovir-based regimen was changed to abacavir, efavirenz and lamivudine with addition of neutral phosphate supplements and calcitriol. On follow-up after 6 months, she had significant improvement in her symptoms as well as in the bone mineral density at the lumbar spine (33.2%), femoral neck (27.6%), trabecular bone score (13.2%) and reduction in the buckling ratio at the narrow neck (6.3%), inter-trochanteric region (34%) and femoral shaft (28.8%). Tenofovir-induced osteomalacia is encountered in individuals on prolonged treatment with tenofovir. Treatment consists of changing to a non-tenofovir-based regimen, as well as supplementation of phosphate and calcitriol. Treatment results in remarkable improvement in symptoms and most densitometric indices.

Learning points

  • Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) and is a major drug in the treatment of retroviral and hepatitis B infections.

  • Tenofovir-related hypophosphatemic osteomalacia is related to proximal tubulopathy and is not an uncommon occurrence.

  • Treatment mandates changing to a non-tenofovir-based regimen with supplementation of neutral phosphate and calcitriol.

  • Treatment results in a significant improvement in bone mineral density, trabecular bone score and hip geometric parameters.

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Mohammed Anwar Hussain Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Aneez Joseph Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Vinoo Mathew Cherian Department of Orthopaedics, Christian Medical College and Hospital, Vellore, India

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Alok Srivastava Department of Haematology, Christian Medical College and Hospital, Vellore, India

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Kripa Elizabeth Cherian Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Nitin Kapoor Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Thomas Vizhalil Paul Department of Endocrinology, Christian Medical College and Hospital, Vellore, India

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Summary

Although bisphosphonates (BPs) are mainly used for the treatment of osteoporosis and are generally safe, long-term use and more dosage as utilised in malignant conditions may be associated with the rare adverse event of an atypical femoral fracture (AFF). Occasionally, the risk of developing an AFF persists long after BPs are withdrawn. A 39-year-old woman who underwent chemotherapy and an autologous stem cell transplantation for multiple myeloma presented to us with history of pain in the left thigh. She had received multiple doses of oral and parenteral BPs for about 10 years in view of the underlying myeloma with osteoporosis. Her investigations showed a suppressed CTX of 192 pg/mL, and radiograph of pelvis displayed thickened cortices with beaking of the left femoral shaft, which was suggestive of an AFF. Following discontinuation of BPs, she underwent prophylactic intra-medullary nailing with which her symptoms improved. Five years later, she presented with similar complaints on the right side. Investigations showed that her bone turnover continued to be suppressed with Cross linked C- Telopeptide of type 1 collagen (CTX) of 165 pg/mL and an X-ray done showed AFF on the right side despite being off BPs. A second intra-medullary nailing was done and on follow-up, she has been symptom-free and independent in her daily activities. Discontinuation of BPs may not prevent the incident second AFF and, therefore, thus warranting long-term follow-up.

Learning points

  • Regular screening and follow-up of patients who receive long-term bisphosphonate (BP) therapy should be done.

  • Discontinuation of BPs does not preclude the possibility of repeated occurrence of a second AFF.

  • Long-term BP therapy warrants regular monitoring and follow-up should an AFF occur

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Jenny S W Yun Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

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Chris McCormack Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

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Michelle Goh Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

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Cherie Chiang Department of Internal Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
University of Melbourne, Parkville, Victoria, Australia

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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.

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David Kishlyansky Division of Internal Medicine, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

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Gregory Kline Divison of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

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Amita Mahajan Divison of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

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Konstantin Koro Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada

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Janice L Pasieka Divison of Endocrine surgery, Surgical Oncology and Endocrinology, Department of Surgery, University of Calgary, Calgary, Alberta, Canada

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Patrick Champagne Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada

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Summary

An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC)/paraganglioma is the cause of ectopic Cushing’s syndrome (CS) in 5.2% of cases reported in the literature. We present a previously healthy 43-year-old woman admitted to our hospital with cushingoid features and hypertensive urgency (blood pressure = 200/120 mmHg). Her 24-h urinary free cortisol was >4270 nmol/day (reference range (RR) = 100–380 nmol/day) with a plasma ACTH of 91.5 pmol/L (RR: 2.0–11.5 pmol/L). Twenty-four-hour urinary metanephrines were increased by 30-fold. Whole-body CT demonstrated a 3.7-cm left adrenal mass with a normal-appearing right adrenal gland. Sellar MRI showed a 5-mm sellar lesion. MIBG scan revealed intense uptake only in the left adrenal mass. She was managed pre-operatively with ketoconazole and phenoxybenzamine and underwent an uneventful left laparoscopic adrenalectomy, which resulted in biochemical resolution of her hypercortisolemia and catecholamine excess. Histology demonstrated a PCC (Grading System for Adrenal Pheochromocytoma and Paraganglioma score 5) with positive ACTH staining by immunohistochemistry. A PCC gene panel showed no mutations and there has been no evidence of recurrence at 24 months. This case highlights the difficult nature of localizing the source of CS in the setting of a co-existing PCC and sellar mass.

Learning points

  • An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC) is an important item to be considered in all patients presenting with ectopic Cushing’s syndrome (CS).

  • In exceptionally rare cases, patients with ectopic CS may present with multiple lesions, and a systematic approach considering all potential sources is crucial to avoid misdiagnosis.

  • CS with a large adrenal mass but lacking contralateral adrenal atrophy should raise suspicion of an ACTH-dependent process.

  • In patients with clinical suspicion of PCC, clinicians should be mindful of the use of steroids and beta-blockers without appropriate alpha blockade as they may precipitate an adrenergic crisis.

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Pranav Gupta Division of Endocrinology, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA

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Karen Loechner Division of Endocrinology, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA
Division of Endocrinology, Department of Pediatrics, Connecticut Childrens Medical Center, Farmington, Connecticut, USA

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Briana C Patterson Division of Endocrinology, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA
Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, Atlanta, Georgia, USA

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Eric Felner Division of Endocrinology, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA

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Summary

Insulinomas are a rare cause of persistent hypoglycemia in a previously healthy child. In addition to symptoms of hypoglycemia, individuals with insulinomas usually present with a history of incessant caloric intake and weight gain due to a constant need to counter hypoglycemia. In addition to an extensive review of the literature, we report the first case of an insulinoma coexisting with reduced appetite secondary to anorexia nervosa in an adolescent female.

Learning points

  • Eliciting a detailed family history is important in hypoglycemia cases.

  • Obtaining a thorough dietary intake, weight history, and menstrual cycles (in females) and considering a psychiatric consultation for an eating disorder when indicated.

  • Although rare in the pediatric population, multiple endocrine neoplasia type 1 syndrome should be considered in the evaluation of children and adolescents with hypoglycemia who also have a family history of pituitary, pancreatic, and/or parathyroid endocrinopathies.

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Liza Das Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Usha Singh Department of Ophthalmology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Bhanu Malhotra Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Sanjay Kumar Bhadada Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Pulkit Rastogi Department of Histopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Paramjeet Singh Department of Radiology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Pinaki Dutta Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Sameeksha Tadepalli Department of Ophthalmology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

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Summary

Thyroid eye disease (TED) is the most common extra-thyroidal manifestation in Graves’ disease (GD). Additional/concurrent/synchronous pathologies may be present, especially in elderly patients who present with atypical features such as non-axial (or eccentric) proptosis, absence of lid lag and restricted superior extra-ocular movements. A 70-year-old female presented with progressive proptosis of her left eye and diplopia. She was diagnosed with GD a year prior and initiated on carbimazole. On examination, she had eccentric proptosis, restricted superior extra-ocular movements and a palpable mass in the supero-temporal quadrant of the left eye. Her T3 (1.33 ng/mL) and T4 (8.85 µg/dL) were normal with carbimazole. Thyroid-stimulating hormone (TSH)-receptor antibody was positive (3.15 IU/L, reference range <1.75). MRI revealed an enhancing lesion infiltrating the left superior rectus, with concurrent characteristic muscle belly involvement bilaterally. Orbital biopsy showed atypical lymphoid cells (CD20+), suggesting marginal zone lymphoma. CT thorax and abdomen, fluorodeoxyglucose-positron emission tomography and bone marrow examination were normal. The patient was administered orbital radiotherapy for her localised lymphoma and carbimazole was continued. TED is the most common cause of orbital involvement overall and in GD. However, additional or alternative pathology may be present which requires evaluation. MRI can be a useful adjunct in these patients. Orbital lymphoma needs to be staged with workup for disseminated disease. Radiotherapy is the treatment of choice for localized disease. The index case provides evidence for synchronous presentation of dual pathology and highlights the importance of astute clinical examination as well as keeps a low threshold for MRI in selected cases.

Learning points

  • Thyroid eye disease can co-exist with other ocular pathology, especially in elderly individuals.

  • Eccentric proptosis, absent lid lag and restriction of eye movements (suggesting tendon involvement) should alert towards the presence of alternative pathology.

  • Orbital imaging using MRI not only has greater sensitivity in diagnosing radiologically bilateral disease in patients who have unilateral involvement clinically but is also useful to identify concurrent neoplasms.

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Farooq Khan Department of Endocrinology, Tipperary University Hospital, Clonmel, Co. Tipperary, Ireland

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Mary Jane Brassill Department of Endocrinology, Tipperary University Hospital, Clonmel, Co. Tipperary, Ireland

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Summary

There is emerging evidence of an association between COVID-19 vaccination and subacute thyroiditis. We present the case of a 42-year-old female healthcare worker who was diagnosed with subacute thyroiditis 4 days after receiving her second dose of Pfizer-BioNTech vaccine. Her clinical course followed the classical pattern for thyroiditis with spontaneous return to euthyroidism at 6 months post-presentation. The autoimmune/inflammatory syndrome induced by adjuvants has been implicated as a cause of autoimmune conditions post-vaccination and is a potential mechanism for subacute thyroiditis in our case.

Learning points

  • Subacute thyroiditis should be considered in all patients who receive any kind of vaccine for COVID-19 and subsequently develop symptoms or signs of hyperthyroidism or neck pain.

  • Subacute thyroiditis is a self-limiting condition, and recognising it is important as no specific thyroid treatment (antithyroid drugs or thyroid hormone replacement) is necessary for most patients.

  • The autoimmune/inflammatory syndrome induced by adjuvants may be an under-recognised cause of endocrinopathies and should particularly be considered post-vaccination.

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