Patient Demographics
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Summary
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce osmotic diuresis by inhibiting the proximal renal tubular reabsorption of the filtered glucose load, which in turn can occasionally lead to severe dehydration and hypotension amidst other adverse effects. We present a case of a 49-year-old man with type 2 diabetes mellitus (T2D) on canagliflozin, a SGLT2i. The patient was brought to the emergency room following a motor vehicle accident. He was confused and had an altered mental status. His blood alcohol and urine toxicology screens were negative. Initial investigations revealed that he had severe hyponatremia with euglycemic ketoacidosis. The adverse condition was reversed with close monitoring and timely management, and the patient was eventually discharged. This is the first report to suggest hyponatremia as a potentially serious adverse effect following SGLT2i therapy. Its impact on the renal tubule handling of sodium and water is not yet well characterized. While further studies are warranted to understand better the pathophysiological mechanisms associated with SGLT2i-induced adverse effects, timely dose reduction or perhaps even its temporary discontinuation may be recommended to prevent complications.
Learning points
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Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are usually well-tolerated, but some serious adverse effects have been documented.
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Our case report suggests hyponatremia as a potential, rare side effect of SGLT2i and makes physicians aware of the occurrence of such life-threatening but preventable complications.
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Timely and close monitoring of the patient, with temporary discontinuation of this drug, may be recommended towards effective management.
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Studies demonstrating a comprehensive understanding of SGLT2i-related electrolyte derangements are warranted.
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Differentiated thyroid cancers generally have favorable prognoses, though follicular thyroid cancer is overall associated with a worse prognosis due in part to increased incidence of distant metastasis. We report a case of a 51-year-old woman with a history of widely invasive follicular thyroid carcinoma treated with a total thyroidectomy, radioactive iodine and external beam radiation. Five and a half years following her surgery, she was found to have an axillary lymph node mass, multiple lung masses, and a hilar mass in the setting of declining thyroglobulin (Tg) antibodies. Her metastases were initially thought to be due to a primary lung adenocarcinoma given a neoplastic cell immunophenotype that included an absence of Tg expression and co-expression of TTF-1 and Napsin A. However, PAX8 expression demonstrated that the axillary and hilar metastases were actually thyroid in origin rather than lung. Axillary metastases in differentiated thyroid carcinoma are exceedingly rare and previous reports have typically involved widely disseminated disease with extensive neck lymphadenopathy. With a decline in Tg antibodies levels in high-risk patients, one should consider progression and loss of differentiation of thyroid carcinoma rather than a response to treatment.
Learning points:
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Axillary metastases in differentiated thyroid carcinoma are uncommon.
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In patients with high-risk thyroid carcinomas, a decline in thyroglobulin antibody may not signal disease improvement, but rather a progression to a poorly differentiated form of cancer.
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PAX8 staining can be used to differentiate thyroid carcinomas from lung adenocarcinomas.
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Summary
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant condition characterized by parathyroid, anterior pituitary and enteropancreatic endocrine cell tumors. Neuroendocrine tumors occur in approximately in 5–15% of MEN1 patients. Very few cases of ovarian NETs have been reported in association with clinical MEN1 and without genetic testing confirmation. Thirty-three-year-old woman with MEN1 was found to have right adnexal mass on computed tomography (CT). Attempt at laparoscopic removal was unsuccessful, and mass was removed via a minilaparotomy in piecemeal fashion. Pathology showed ovarian NET arising from a teratoma. Four years later, patient presented with recurrence involving the pelvis and anterior abdominal wall. She was treated with debulking surgery and somatostatin analogs (SSAs). Targeted DNA sequencing analysis on the primary adnexal mass as well as the recurrent abdominal wall tumor confirmed loss of heterozygosity (LOH) at the MEN1 gene locus. This case represents to our knowledge, the first genetically confirmed case of ovarian NET arising by a MEN1 mechanism in a patient with MEN1. Extreme caution should be exercised during surgery as failure to remove an ovarian NET en masse can result in peritoneal seeding and recurrence. For patients with advanced ovarian NETs, systemic therapy options include SSAs, peptide receptor radioligand therapy (PRRT) and novel agents targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF).
Learning points:
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Ovarian NET can arise from a MEN1 mechanism, and any adnexal mass in a MEN1 patient can be considered as a possible malignant NET.
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Given the rarity of this disease, limited data are available on prognostication and treatment. Management strategies are extrapolated from evidence available in NETs from primaries of other origins.
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Care should be exercised to remove ovarian NETs en bloc as failure to do so may result in peritoneal seeding and recurrence.
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Treatment options for advanced disease include debulking surgery, SSAs, TKIs, mTOR inhibitors, PRRT and chemotherapy.
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Division of Pediatric Endocrinology, Hurley Children’s Hospital, Flint, Michigan, USA
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Division of Pediatric Hematology and Oncology, Hurley Children’s Hospital, Flint, Michigan, USA
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Summary
A 6-year-old female presented with chronic intermittent abdominal pain for 1 year. She underwent extensive investigation, imaging and invasive procedures with multiple emergency room visits. It caused a significant distress to the patient and the family with multiple missing days at school in addition to financial burden and emotional stress the child endured. When clinical picture was combined with laboratory finding of macrocytic anemia, a diagnosis of hypothyroidism was made. Although chronic abdominal pain in pediatric population is usually due to functional causes such as irritable bowel syndrome, abdominal migraine and functional abdominal pain. Hypothyroidism can have unusual presentation including abdominal pain. The literature on abdominal pain as the main presentation of thyroid disorder is limited. Pediatricians should exclude hypothyroidism in a patient who presents with chronic abdominal pain. Contrast to its treatment, clinical presentation of hypothyroidism can be diverse and challenging, leading to a delay in diagnosis and causing significant morbidity.
Learning points:
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Hypothyroidism can have a wide range of clinical presentations that are often nonspecific, which can cause difficulty in diagnosis.
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In pediatric patients presenting with chronic abdominal pain as only symptom, hypothyroidism should be considered by the pediatricians and ruled out.
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In pediatric population, treatment of hypothyroidism varies depending on patients’ weight and age.
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Delay in diagnosis of hypothyroidism can cause significant morbidity and distress in pediatrics population.
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Summary
Metformin is recommended as the first-line agent for the treatment of type 2 diabetes. Although this drug has a generally good safety profile, rare but potentially serious adverse effects may occur. Metformin-associated lactic acidosis, although very uncommon, carries a significant risk of mortality. The relationship between metformin accumulation and lactic acidosis is complex and is affected by the presence of comorbid conditions such as renal and hepatic disease. Plasma metformin levels do not reliably correlate with the severity of lactic acidosis. We present a case of inadvertent metformin overdose in a patient with both renal failure and hepatic cirrhosis, leading to two episodes of lactic acidosis and hypoglycemia. The patient was successfully treated with hemodialysis both times and did not develop any further lactic acidosis or hypoglycemia, after the identification of metformin tablets accidentally mixed in with his supply of sevelamer tablets. Early initiation of renal replacement therapy is key in decreasing lactic acidosis-associated mortality.
Learning points:
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When a toxic ingestion is suspected, direct visualization of the patient’s pills is advised in order to rule out the possibility of patient- or pharmacist-related medication errors.
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Though sending a specimen for determination of the plasma metformin concentration is important when a metformin-treated patient with diabetes presents with lactic acidosis, complex relationships exist between metformin accumulation, hyperlactatemia and acidosis, and the drug may not always be the precipitating factor.
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Intermittent hemodialysis is recommended as the first-line treatment for metformin-associated lactic acidosis (MALA).
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An investigational delayed-release form of metformin with reduced systemic absorption may carry a lower risk for MALA in patients with renal insufficiency, in whom metformin therapy may presently be contraindicated.
