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Rady Children’s Hospital, University of California, San Diego, California, USA
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Summary
A 6.6-year-old female presented to endocrinology with precocious puberty for evaluation and management. Workup was initiated, and a diagnosis of central precocious puberty was confirmed. A decision was made to initiate pubertal blockade using gonadotropin-releasing hormone agonist (GnRHa) therapy with depot leuprolide acetate injections every 3 months. The patient received the first depot leuprolide acetate injection in the right ventrogluteal area. Six hours following the injection, the patient was reported to be inconsolable in pain, which was localized to the right hip site of the earlier injection and associated with a refusal to ambulate. The pain and discomfort continued to progress over the next 24 h despite an alternating regimen of Tylenol and ibuprofen prompting admission to the emergency department. Vital signs demonstrated a low-grade fever and elevated C-reactive protein. An ultrasound of the right hip demonstrated fluid accumulation within the joint. Over the next week, the patient was unable to walk independently and required assistance for activities of daily living. By 2 weeks after the injection, the pain began to remit, and the patient resumed activities of daily living. Following consultation with allergy, a decision was made to continue GnRHa suppressive therapy with an alternative analog (Triptodur). The patient tolerated subsequent treatment without reaction.
Learning points
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Although gonadotropin-releasing hormone agonists (GnRHa) have a generally good safety profile, there is a history of both local and systemic hypersensitivity reactions associated with their use.
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Despite the long-acting formulation of depot leuprolide acetate, the systemic reaction in this case appears to be self-limited.
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Discontinuation of therapy or a change to an alternative formulation of GnRHa analog should be considered based on the need for therapy versus the potential risk of rechallenge.
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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
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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.
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Herbal medications are freely available online, even without a prescription.
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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.
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Heavy metals are present in toxic levels in the drugs, causing complications.
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Lead is the most common heavy metal found in such herbal medicines.
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Lead poisoning leads to anemia and other systemic complications which could have been fatal if not found in time.
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St Vincent’s Clinical School, University of New South Wales, Sydney, Australia
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Cancer Genetics Unit, Kolling Institute of Medical Research, Sydney, Australia
Northern Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, Australia
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Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, Australia
Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Sydney, Australia
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Cancer Genetics Unit, Kolling Institute of Medical Research, Sydney, Australia
Northern Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, Australia
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Summary
RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented efficacy compared to previous multi-kinase treatments. Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm usually driven by somatic BRAF mutations, resulting in dysregulated MAPK signalling. We describe a 22-year-old woman with metastatic MTC to regional lymph nodes, lung and liver. Tumour tissue harboured a somatic pathogenic RET variant p.(M918T) and selpercatinib was commenced. She experienced sustained clinical, biochemical and radiological responses. Two years later, she developed rapidly progressive apical lung nodules, prompting biopsy. Histopathology demonstrated LCH with a rare BRAF variant p.(V600_K601>D). The lung nodules improved with inhaled corticosteroids. We hypothesize that selective pressure from RET blockade may have activated a downstream somatic BRAF mutation, resulting in pulmonary LCH. We recommend continued vigilance for neoplasms driven by dysregulated downstream MAPK signalling in patients undergoing selective RET inhibition.
Learning points
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Patients with RET-altered MTC can experience rapid disease improvement and sustained disease stability with selective RET blockade (selpercatinib).
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LCH is a clonal neoplasm driven by MAPK activation, for which the most common mechanism is BRAF mutation.
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Both MTC and pulmonary LCH are driven by dysregulated MAPK signalling pathway activation.
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We hypothesise that the RET-specific inhibitor selpercatinib may have caused the activation of dormant LCH secondary to selective pressure and clonal proliferation.
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Summary
IgG4-related disease is a multiorgan disorder in which nodules and hypertrophic lesions are observed simultaneously, or separately, in areas including the pancreas, liver, lungs, salivary glands, thyroid glands, and pituitary glands. IgG4-related hypophysis is one of several IgG4-related diseases and is characterized by pituitary gland and pituitary stalk thickening, various degrees of hypopituitarism, and increased serum IgG4 levels. Steroid therapy is effective for patients with IgG4-related hypophysis, but the reported effectiveness of steroid therapy for restoring pituitary function differs between studies. Following an episode of autoimmune pancreatitis 10 years prior, enlargement of the pituitary gland and stalk along with panhypopituitarism and polyuria developed in a 73-year-old male. A high serum IgG4 level and biopsy of the submandibular gland showing infiltration of IgG4-positive plasma cells led to a clinical diagnosis of IgG4-related hypophysitis. Prednisolone treatment reduced the swelling of the pituitary gland and stalk and improved anterior pituitary function. Although arginine vasopressin secretion remained insufficient, polyuria was relieved and kept in remission even after prednisolone treatment was completed. This is the first reported case in which prednisolone was able to maintain both normal anterior pituitary function and remission of polyuria caused by IgG4-related hypophysitis. IgG4-related hypophysitis has previously been associated with a relapse of symptoms during treatment. However, the patient reported in this case study remained in remission for over 3 months after completion of steroid treatment and should be monitored closely for changes in pituitary function.
Learning points
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Steroid therapy is the first-line therapy for pituitary dysfunction and pituitary stalk swelling in IgG4-related hypophysitis.
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In this case, although posterior pituitary function remained insufficient, polyuria was relieved and kept in remission for over 3 months even after prednisolone treatment was completed.
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IgG4-related hypophysitis has been associated with the relapse of symptoms during steroid tapering, and changes in pituitary function and symptoms should be monitored closely.
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When we encounter cases of adrenal insufficiency and polyuria during observation of autoimmune pancreatitis or other IgG4-related disease, we should consider the possibility of IgG4-related hypophysitis in mind.
Innovation and Research Center of Endocrinology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
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Summary
Symptoms of primary adrenal insufficiency (PAI) are commonly nonspecific, causing the disease to be misdiagnosed or often delayed, and patients may present to the hospital with a life-threatening crisis. Previous case reports have documented that patients in this condition often require lifelong glucocorticoid replacement therapy. This study aimed to present a noteworthy outcome of PAI caused by adrenal tuberculosis infection, demonstrating complete recovery after six months of glucocorticoid replacement therapy. A 38-year-old Indonesian man presented to the endocrinology clinic in a tertiary hospital with a chief complaint of epigastric pain. The patient experienced nausea, vomiting, loss of consciousness, weight loss, excessive sweat, decreased appetite, weakness, and dizziness in the past 2 weeks. Laboratory examinations revealed hyponatremia, elevated adrenocorticotropic hormone, and suppressed morning plasma cortisol level. A non-contrast-enhanced abdominal MRI showed unilateral right-side adrenal enlargement and calcification. The patient’s Mantoux test was positive. Corticosteroids and anti-tuberculosis therapy were administered. After 6 months, hydrocortisone was discontinued due to the patient’s good clinical condition and normal morning plasma cortisol levels. After a 1-year follow-up, the patient remained asymptomatic with normal cortisol levels. We hypothesized several reasons for this unique outcome: (i) the patient was relatively young compared to previous cases, suggesting an adequate immune system may play a role; (ii) despite a 1-month delay in diagnosis and treatment, the absence of skin hyperpigmentation suggested an acute presentation, potentially contributing to the favorable outcome; and (iii) the absence of comorbidities potentially positively impacted the patient's outcome.
Learning points
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Symptoms of adrenal insufficiency are often nonspecific and may only become apparent once significant damage has occurred to the adrenal gland.
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Clinical adjustments and a comprehensive understanding of epidemiological knowledge are necessary for diagnosing patients with endocrine diseases in limited-resource settings.
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Complete recovery in primary adrenal insufficiency caused by tuberculosis infection might be due to younger age, acute presentation, and absence of comorbidities
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Ghent University, Ghent, Belgium
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Summary
Mitotane is used for treatment of advanced adrenocortical carcinoma. It is administered when the carcinoma is unresectable, metastasized, or at high-risk of recurrence after resection. In addition, mitotane is considered to have direct adrenolytic effects. Because of its narrow therapeutic–toxic range, therapeutic drug monitoring (TDM) is warranted. In 2020, a left-sided adrenal gland tumor was found (5.8 cm) in a 38-year-old man. Considering the size of this lesion and inability to exclude an adrenocortical carcinoma on imaging, a laparoscopic adrenalectomy was performed. Histopathologic examination determined presence of an adrenocortical carcinoma (pT2N0M0 ENSAT stadium II; ki67 10–15%). There was no evidence for residual or metastatic disease but given the high risk of recurrence, adjuvant therapy with mitotane was initiated. During TDM, a sudden and spuriously high level of mitotane was observed but without signs or symptoms of toxicity. After exploration, it was found that this high concentration was completely due to uncontrolled hypertriglyceridemia. After correction thereof, mitotane levels were again in the therapeutic range. This observation underscores the importance of TDM sampling in a fasting state with concurrent control of prevalent or incident dyslipidemia.
Learning points
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TDM of mitotane is advocated to achieve therapeutic levels while avoiding toxicity. For correct TDM, sampling should be done at least 12 h after last intake of mitotane.
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Although sampling in fasting conditions in not explicitly mentioned in the guidelines, fasting state should be considered as elevated serum triglyceride levels might cause spuriously high mitotane levels.
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In patients undergoing treatment with mitotane and presenting with too high or unexplained fluctuating mitotane levels without signs or symptoms of toxicity, hypertriglyceridemia as a possible cause should be investigated.
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If dyslipidemia occurs in patients under mitotane treatment, other causes than mitotane (e.g. alcohol abuse and diabetes) should be considered and appropriate treatment should be initiated.
School of Cardiovascular Medicine & Sciences, King's College London, London, UK
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School of Cardiovascular Medicine & Sciences, King's College London, London, UK
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Summary
A Caucasian man in his 60s with recent diagnosis of metastatic renal cell carcinoma presented to the emergency department with a 5-day history of severe polyuria, polydipsia and fatigue and 1-day history of confusion, abdominal pain, nausea and vomiting. Investigations revealed an overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS). He had received the first dose of immunotherapy with nivolumab and ipilimumab 3 weeks prior to this attendance. New-onset type 1 diabetes (T1DM) was confirmed based on the clinical features at presentation, seropositivity for glutamic acid decarboxylase antibodies and significant insulin deficiency. He is currently on a multiple daily injections of insulin and uses intermittent-scanned glucose monitoring. Given the irreversible impact on beta-cell function and clinical response with insulin resulting in improved diabetes control, immunotherapy was resumed for his metastatic cancer with good radiological response. Although rare, new-onset T1DM can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes.
Learning points
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Although rare, new onset of T1DM after immunotherapy can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes and normal glycaemic parameters.
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Due to the irreversible destruction of beta-cells, treatment with steroids is not indicated in contrast to other settings such as immunotherapy-induced hypophysitis.
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Presence of low c-peptide levels post-acute presentation is indicative of an irreversible impact on beta-cell function and supports resuming immunotherapy given the significant benefits on cancer prognosis.
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Clinicians must maintain a high index of suspicion in regards to diagnosis and management of new-onset type 1 diabetes and advice patients on reporting symptoms suggestive of diabetes and/or diabetes-related hyperglycaemic emergencies.
Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy
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Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy
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Summary
Psoriasis is often associated with abdominal obesity and type-2 diabetes (T2D). The inflammatory process in psoriasis can target adipose tissue depots, especially those surrounding the heart and coronary arteries, exposing to an increased risk of cardiovascular diseases. A 50-year-old female patient referred to us for abdominal obesity and T2D, which were not controlled with lifestyle modifications. She had suffered from psoriasis for some years and was treated with guselkumab, without success. Epicardial adipose tissue (EAT) attenuation and pericoronary adipose tissue (PCAT) attenuation for each coronary, defined as mean attenuation expressed in Hounsfield unit (HU), were assessed by routine coronary computed tomography angiography. At baseline, EAT attenuation was −80 HU and PCAT attenuation of the right coronary artery (RCA) was −68 HU, values associated with an increased cardiac mortality risk. Psoriasis area and severity index (PASI) was 12.0, indicating severe psoriasis, while dermatology life quality index (DLQI) was 20, indicating a negative effect on the patient’s life. Semaglutide (starting with 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 16 weeks, and then to 1 mg/week) was started. After 10 months, semaglutide treatment normalized glycated hemoglobin and induced weight loss, particularly at abdominal level, also followed by a reduction in computed tomography-measured EAT volume. EAT attenuation and PCAT attenuation of RCA decreased, showing an important reduction of 17.5 and 5.9% respectively, compared with baseline. PASI and DLQI decreased by 98.3 and 95% respectively, indicating an improvement in psoriasis skin lesions and an important amelioration of the patient’s quality of life, compared with baseline.
Learning points
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Psoriasis patients affected by obesity and type-2 diabetes (T2D) are often resistant to biologic therapies.
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Psoriasis is often associated with abdominal obesity, T2D, and cardiovascular diseases (CVD), given their shared inflammatory properties and pathogenic similarities.
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Epicardial adipose tissue (EAT) inflammation can cause the distinctive pattern of CVD seen in psoriasis.
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EAT and pericoronary adipose tissue (PCAT) attenuation, assessed by routine coronary computed tomography angiography (CCTA), can be used as biomarkers of inflammation and allow monitoring of medical anti-inflammatory therapies.
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The actions of semaglutide to reduce energy intake, improve glycemic control, and produce effective weight loss, particularly at the visceral fat depot level, can diminish adipose tissue dysfunction, reduce EAT attenuation and PCAT attenuation of the right coronary artery (RCA) and concomitantly ameliorate the clinical severity of psoriasis.
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Semaglutide therapy may be considered in psoriasis patients affected by T2D and abdominal obesity, despite low cardiovascular risk by traditional risk scores, who are resistant to biologic therapies.
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Faculdade de Medicina, Universidade de Coimbra, Portugal
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Summary
We report a case of a woman with a diagnosis of breast cancer who unintentionally started gaining weight, feeling tired, and constipated 44 weeks after the initiation of trastuzumab. Hypothyroidism secondary to an autoimmune thyroiditis associated with trastuzumab was diagnosed, the first case described in Portugal and the fourth case described worldwide. Our intention regarding the publication of this case report is to alert the clinicians treating people with trastuzumab that they should ask the patients about symptoms of hypothyroidism and should screen the thyroid function of the patients before, during, and after the initiation of trastuzumab.
Learning points
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Trastuzumab is a humanized MAB used in HER2-positive breast and gastric cancer.
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Trastuzumab-associated autoimmune thyroid disease (AITD) is rare (incidence rate in an RCT of 0.3%).
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Manifestations of autoimmune thyroiditis associated with trastuzumab resemble those of hypothyroidism in other clinical contexts, but the presence of goiter is highlighted as a reason for medical evaluation. Biochemically, it is characterized by an increased thyroid-stimulating hormone (TSH) with or without a low FT4/FT3, and sonographically with a pattern of thyroiditis.
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The treatment consists of levothyroxine, in a dose of 1.6–1.8 µg/kg/day, with re-evaluation of the thyroid function in 4–6 weeks.
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We report the first case of autoimmune thyroiditis secondary to trastuzumab in Portugal.
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It is important to evaluate the thyroid function before, during, and after the initiation of this therapeutic agent.