Publication Details > Case Report Type > Insight into disease pathogenesis or mechanism of therapy
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Search for other papers by Rigya Arya in
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Banting and Best Diabetes Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Summary
Central diabetes insipidus (CDI) is a rare manifestation of acute myeloid leukemia (AML) with unclear etiology. When present, CDI in AML has most often been described in patients with chromosome 3 or 7 aberrations and no abnormalities on brain imaging. In this case, we present a woman with newly diagnosed AML t(12;14)(p12;q13) found to have diabetes insipidus (DI) with partial anterior pituitary dysfunction and abnormal brain imaging. While in hospital, the patient developed an elevated serum sodium of 151 mmol/L with a serum osmolality of 323 mmol/kg and urine osmolality of 154 mmol/kg. On history, she reported polyuria and polydipsia for 5 months preceding hospitalization. Based on her clinical symptoms and biochemistry, she was diagnosed with DI and treated using intravenous desmopressin with good effect; sodium improved to 144 mmol/L with a serum osmolality of 302 mmol/kg and urine osmolality of 501 mmol/kg. An MRI of the brain done for the assessment of neurologic involvement revealed symmetric high-T2 signal within the hypothalamus extending into the mamillary bodies bilaterally, a partially empty sella, and loss of the pituitary bright spot. A pituitary panel was completed which suggested partial anterior pituitary dysfunction. The patient’s robust improvement with low-dose desmopressin therapy along with her imaging findings indicated a central rather than nephrogenic cause for her DI. Given the time course of her presentation with respect to her AML diagnosis, MRI findings, and investigations excluding other causes, her CDI and partial anterior pituitary dysfunction were suspected to be secondary to hypothalamic leukemic infiltration.
Learning points
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Leukemic infiltration of the pituitary gland is a rare cause of central diabetes insipidus (CDI) in patients with acute myeloid leukemia (AML).
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Patients with AML and CDI may compensate for polyuria and prevent hypernatremia with increased water intake.
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AML-associated CDI can require long-term desmopressin treatment, independent of AML response to treatment.
Search for other papers by Eimear Mary O’Donovan in
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Search for other papers by Maria Michelle Byrne in
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Summary
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.
Learning points
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These cases highlight the rare coexistence of autoimmune diabetes and MODY.
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Deterioration of glycaemic control in subjects with MODY diabetes should highlight the emergence of autoantibodies.
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One should revise and update the family history as the diagnosis of MODY was made after the development of diabetes in offspring.
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Understanding the spectrum of diabetes allows for precision medicine.
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Search for other papers by Hamza Akhtar in
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Search for other papers by Nissa Blocher in
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Search for other papers by Catherine Anastasopoulou in
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Summary
Graves’ disease can have multiple cardiac manifestations. A rare complication is that of severe mitral regurgitation secondary to mitral valve chordae rupture, due to both compromise of valve integrity by deposition of glycosaminoglycans and the hemodynamic stresses of thyrotoxicosis. Pregnancy, with its related hemodynamic changes, is another setting in which mitral valve chordae rupture has occasionally been documented. We present a unique case of a 36-year-old female with uncontrolled Graves’ disease who presented during pregnancy at 13 weeks gestation with atrial flutter and features of congestive heart failure. Echocardiogram found severe mitral regurgitation secondary to a ruptured mitral chord. She was treated conservatively with diuresis and ultimately delivered her baby without complication at 28 weeks when she had preterm premature rupture of membranes. She is currently on methimazole and propranolol and pending definitive management of her Graves’ disease. This represents not only a rare cardiac complication in a patient with Graves’ disease but also is the first in the literature, to our knowledge, which describes this complication in a pregnant patient with Graves’ disease.
Learning points
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Thyroid disease can have multiple effects on the heart through hemodynamic and structural changes and can result in heart failure, arrhythmias, valvular disease, and pulmonary hypertension.
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Graves’ disease can cause glycosaminoglycan deposition in valvular tissue resulting in fragile leaflets that can rupture with little stress.
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Pregnancy and thyrotoxicosis have similar hemodynamic consequences with increased cardiac output and reduced systemic vascular resistance.
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Be vigilant in those with hyperthyroidism with a new murmur or features of acute heart failure, as a ruptured valve chord can result in increased morbidity and mortality if not recognized and addressed quickly.
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Search for other papers by Catherine Nelson-Piercy in
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Summary
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.
Learning points
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Clinicians should maintain a wide differential when assessing women who are unwell with COVID-19 in pregnancy.
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Complications such as starvation ketoacidosis are rare but life-threatening.
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An awareness of such complications facilitates early identification of the condition, and involvement of appropriate specialists who can initiate optimal and timely management.
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In the context of pregnancy, where ketoacidosis poses a threat to the mother or baby, prompt management and resolution may avoid preterm delivery.
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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.
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Multidisciplinary input supports the delivery of best practice and care for the patients.
Saint Louis University School of Medicine, St. Louis, Missouri, USA
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Summary
We identified an adolescent young woman with new-onset diabetes. Due to suspicious family history, she underwent genetic testing for common monogenic diabetes (MODY) genes. We discovered that she and her father carry a novel variant of uncertain significance in the HNF1A gene. She was successfully transitioned from insulin to a sulfonylurea with excellent glycemic control. Based on her family history and successful response to sulfonylurea, we propose that this is a novel pathogenic variant in HNF1A. This case highlights the utility of genetic testing for MODY, which has the potential to help affected patients control their diabetes without insulin.
Learning points
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HNF1A mutations are a common cause of monogenic diabetes in patients presenting with early-onset diabetes and significant family history.
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Genetic testing in suspected patients allows for the identification of mutations causing monogenic diabetes.
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First-degree relatives of the affected individual should be considered for genetic testing.
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The use of sulfonylurea agents in patients with HNF1A-MODY can reduce dependence on insulin therapy and provide successful glycemic control.
Department of Internal Medicine, Kilimanjaro Christian Medical University College, Moshi, Tanzania
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Department of Internal Medicine, Kilimanjaro Christian Medical University College, Moshi, Tanzania
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Department of Internal Medicine, Kilimanjaro Christian Medical University College, Moshi, Tanzania
Search for other papers by Elichilia R Shao in
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Summary
Myxedema coma is a severe complication of hypothyroidism, commonly affecting women over 60 years of age, causing slow, progressive multi-organ dysfunction, and mental deterioration. Due to improved diagnostics and treatment of hypothyroidism, myxedema coma has become uncommon. However, it is hardly reported in resource-limited settings. We present an elderly female with a history of total thyroidectomy due to multi-nodular goiter. She presented with features of heart failure, excessive weight gain, and cold sensation. Although the patient was on levothyroxine replacement therapy, her laboratory tests were suggestive of overt primary hypothyroidism. During the course of her hospitalization, she developed subcutaneous bleeding with frank hematuria. This led to an altered mental state and hypotension that were suggestive of myxedema coma. Stroke and pulmonary embolism were ruled out as potential differential diagnoses of her current state. She was treated with a high dose of oral levothyroxine followed by 150 μg of oral levothyroxine daily, which resulted in a favorable outcome despite being a fatal emergency. She was also treated with intravenous hydrocortisone and furosemide. Oral thyroid hormone replacement may be an effective option in those resource-limited settings where intravenous thyroid hormone replacement is not available. However, early diagnosis and treatment with an adequate dose of thyroid hormones are crucial to achieve a favorable outcome.
Learning points
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Myxedema coma is an uncommon complication of hypothyroidism with a fatal outcome.
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The diagnosis of myxedema coma is based on clinical suspicion, especially in patients with hypothyroidism and in the presence of precipitating factors. Although diagnostic and scoring criteria based on clinical, laboratory, and imaging features have been proposed, no consensus has been reached.
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This article shows an alternative treatment option for myxedema coma using oral levothyroxine, which led to a favorable outcome.
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Search for other papers by M G E H Lam in
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Search for other papers by R S van Leeuwaarde in
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Summary
Von Hippel–Lindau’s disease (VHL) is a hereditary tumor syndrome characterized by its prototype lesions, hemangioblastomas, and renal cell carcinomas. Treatment for renal cell carcinomas can ultimately result in long-term dialysis. Pancreatic neuroendocrine tumors (pNET) can also occur in the course of the disease. Currently, peptide receptor radionuclide therapy (PRRT) is the standard treatment for progressive neuroendocrine tumors. However, little is known about treatment with PRRT in patients on dialysis, an infrequent presentation in patients with VHL. We present a 72-year-old man with VHL on hemodialysis and a progressive pNET. He received four cycles of PRRT with a reduced dose. Only mild thrombopenia was seen during treatments. The patient died 9 months after the last PRRT because of acute bleeding in a hemangioblastoma. Hemodialysis is not a limiting factor for PRRT treatment and it should be considered as it seems a safe short-term treatment option for this specific group.
Learning points
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Von Hippel–Lindau disease (VHL) is a complex disease in which former interventions can limit optimal treatment for following VHL-related tumors later in life.
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Metastasized pancreatic neuroendocrine tumors occur as part of VHL disease.
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Peptide receptor radionuclide therapy seems a safe short-term treatment option in patients on hemodialysis.
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Summary
Multiple endocrine neoplasia type 1 NM_001370259.2(MEN1):c.466G>C(p.Gly156Arg) is characterized by tumors of various endocrine organs. We report on a rare, growth hormone-releasing hormone (GHRH)-releasing pancreatic tumor in a MEN1 patient with a long-term follow-up after surgery. A 22-year-old male with MEN1 syndrome, primary hyperparathyroidism and an acromegalic habitus was observed to have a pancreatic tumor on abdominal CT scanning, growth hormone (GH) and insulin-like growth factor 1 (IGF1) were elevated and plasma GHRH was exceptionally high. GHRH and GH were measured before the treatment and were followed during the study. During octreotide treatment, IGF1 normalized and the GH curve was near normal. After surgical treatment of primary hyperparathyroidism, a pancreatic tail tumor was enucleated. The tumor cells were positive for GHRH antibody staining. After the operation, acromegaly was cured as judged by laboratory tests. No reactivation of acromegaly has been seen during a 20-year follow-up. In conclusion, an ectopic GHRH-producing, pancreatic endocrine neoplasia may represent a rare manifestation of MEN1 syndrome.
Learning points
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Clinical suspicion is in a key position in detecting acromegaly.
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Remember genetic disorders with young individuals having primary hyperparathyroidism.
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Consider multiple endocrine neoplasia type 1 syndrome when a person has several endocrine neoplasia.
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Acromegaly may be of ectopic origin with patients showing no abnormalities in radiological imaging of the pituitary gland.
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Department of Anesthesiology and Perioperative Medicine, University Hospital Brussels (VUB), Brussels, Belgium
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Search for other papers by Bert Bravenboer in
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Summary
The pandemic caused by severe acute respiratory syndrome coronavirus 2 is of an unprecedented magnitude and has made it challenging to properly treat patients with urgent or rare endocrine disorders. Little is known about the risk of coronavirus disease 2019 (COVID-19) in patients with rare endocrine malignancies, such as pituitary carcinoma. We describe the case of a 43-year-old patient with adrenocorticotrophic hormone-secreting pituitary carcinoma who developed a severe COVID-19 infection. He had stabilized Cushing’s disease after multiple lines of treatment and was currently receiving maintenance immunotherapy with nivolumab (240 mg every 2 weeks) and steroidogenesis inhibition with ketoconazole (800 mg daily). On admission, he was urgently intubated for respiratory exhaustion. Supplementation of corticosteroid requirements consisted of high-dose dexamethasone, in analogy with the RECOVERY trial, followed by the reintroduction of ketoconazole under the coverage of a hydrocortisone stress regimen, which was continued at a dose depending on the current level of stress. He had a prolonged and complicated stay at the intensive care unit but was eventually discharged and able to continue his rehabilitation. The case points out that multiple risk factors for severe COVID-19 are present in patients with Cushing’s syndrome. ‘Block-replacement’ therapy with suppression of endogenous steroidogenesis and supplementation of corticosteroid requirements might be preferred in this patient population.
Learning points
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Comorbidities for severe coronavirus disease 2019 (COVID-19) are frequently present in patients with Cushing’s syndrome.
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‘Block-replacement’ with suppression of endogenous steroidogenesis and supplementation of corticosteroid requirements might be preferred to reduce the need for biochemical monitoring and avoid adrenal insufficiency.
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The optimal corticosteroid dose/choice for COVID-19 is unclear, especially in patients with endogenous glucocorticoid excess.
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First-line surgery vs initial disease control with steroidogenesis inhibitors for Cushing’s disease should be discussed depending on the current healthcare situation.
Search for other papers by Wouter W. de Herder in
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Summary
The iconic photograph ‘A Jewish giant at home with his parents in the Bronx, N.Y. 1970’ by the famous American photographer Diane Arbus (1923–1971) shows the 2.34 m (7 ft. 8¼ in.) acromegalic giant Eddie Carmel (1936–1972) and his parents in the living room of their New York home. The picture is a typical example of Arbus’ style. The relationship between the artist and the tall subject is described. A growth hormone-secreting pituitary macroadenoma was unsuccessfully treated with two cycles of pituitary radiotherapy achieving a 7000 rad cumulative dose and by incomplete pituitary surgery. Hypopituitarism was treated according to medical standards in the 1960s and 1970s. The giant patient died of increased intracranial pressure and at autopsy a residual acidophil pituitary macroadenoma was found, but also a perisellar meningioma which was most probably induced by the high dose of pituitary radiotherapy. The case report illustrates the possibilities and impossibilities of treating acromegaly 50 years ago and demonstrates the potential risks of high dose pituitary radiotherapy (in acromegaly).
Learning points
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Acromegaly is a very old disease.
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Therapy for acromegaly has evolved over the decades.
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In art museums one can come across artistic impressions of endocrine disorders.
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People suffering from disfiguring endocrine disorders like acromegaly were pre-WW2 ‘exposed’ in theaters and circuses.
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High dose pituitary radiotherapy can be associated with secondary brain tumor formation.