Summary

Human T-cell lymphotropic virus-1 (HTLV-1) causes adult T-cell leukemia and lymphoma (ATLL) and is a rare but important cause of hypercalcemia. A 53-year-old male with HTLV-1-associated myelopathy presented with acute on chronic bilateral lower extremity weakness and numbness. Initial blood work revealed hypercalcemia with corrected calcium of 16.2 mg/dL (8.5–11.5) with normal levels of phosphorus and alkaline phosphatase. Workup for hypercalcemia revealed parathyroid hormone (PTH) of 14 pg/mL (10–65), 25 hydroxy vitamin D at 19.6 ng/mL (30–100), 1,25 dihydroxy vitamin D at 6.7 pg/mL (19.9–79.3), thyroid-stimulating hormone of 1.265 μIU/mL (0.5–5), undetectable PTH-related protein (PTHrP) and lactate dehydrogenase of 433 U/L (100–220). The urine calcium creatinine ratio was 0.388. Reverse transcriptase PCR was positive for HTLV-1 and negative for HTLV-2. Peripheral blood flow cytometry and lymph node biopsy confirmed ATLL. He received treatment with fluids, calcitonin and denosumab after which serum calcium levels fell (nadir: 7.7 mg/dL) and then normalized. Humoral hypercalcemia in this setting is mediated by receptor activator of nuclear factor-kappa B ligand (RANKL), PTHrP and other cytokines. PTHrP levels depend on levels of the TAX gene product, cell type and lymphocyte-specific factors. Thus, a low level, like in our patient, does not rule out HTLV-1 infection/ATLL as the cause of hypercalcemia. Hypercalcemia is known to be responsive to monoclonal antibodies against RANKL given the compound’s role in mediating hypercalcemia in these cases.

Learning points

• Human T-cell lymphotropic virus-1 infection and adult T-cell leukemia and lymphoma are associated with high rates of hypercalcemia and hypercalcemic crises.

• Hypercalcemia in these cases is mediated by osteoclastic bone resorption carried out by several agents including receptor activator of nuclear factor-kappa B ligand, parathyroid hormone-related protein (PTHrP), macrophage inflammatory protein 1 alpha, interleukins, etc. A normal PTHRrP does not rule out humoral hypercalcemia of malignancy in this setting, as indicated by this case.

• Hypercalcemia in such settings is highly responsive to monoclonal antibodies against RANKL given the role the ligand plays in resorptive hypercalcemia.

Summary

Anaphylaxis is a rapidly progressive potentially lethal condition, and epinephrine is the most crucial medication in its treatment. In this study, we present a case of diabetic ketoacidosis in a young woman that was precipitated by the administration of epinephrine to treat anaphylaxis. This patient had diabetes mellitus and poor glycemic control and developed ketoacidosis despite having evidence of ongoing endogenous insulin production and having been treated with exogenous long-acting insulin less than 24 h prior to the event. This is a rare, serious, adverse side effect of life-saving medication. This report demonstrates that the risk of diabetic ketoacidosis should be considered when administering epinephrine to patients with diabetes, even in the absence of complete insulin deficiency.

Learning points

• Epinephrine directly suppresses insulin secretion, stimulates lipolysis, and causes ketone body generation.

• High-dose catecholamine administration can cause unexpected diabetic ketoacidosis in patients with risk factors.

• Early administration of insulin may not protect patients from developing ketoacidosis in the setting of high-dose catecholamine administration.

Summary

Skeletal abnormalities with delayed bone age and decreased linear bone growth are commonly found in children with prolonged juvenile hypothyroidism. However, rachitic bone abnormalities have not been previously reported in children with acquired hypothyroidism. Here, we present a case of newly found rickets in an 8-year-old female with untreated acquired hypothyroidism secondary to Hashimoto’s thyroiditis. Laboratory finding for abnormalities in calcium/phosphorus homeostasis and hormones that regulate skeletal health was normal. Her radiographic anomalies resolved with levothyroxine treatment alone, suggesting that hypothyroidism was the etiology of the rickets. To our knowledge, this is the first case report of rickets associated with long-standing severe acquired hypothyroidism that resolved exclusively with thyroid repletion.

Learning points

• Thyroid hormone plays an important role in bone mineralization.

• Prolonged hypothyroidism can result in rachitic bone abnormalities noted on radiographs.

• Hypothyroidism should be considered in the evaluation of a child with rickets.

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

• 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.

• Graves’ disease can cause glycosaminoglycan deposition in valvular tissue resulting in fragile leaflets that can rupture with little stress.

• Pregnancy and thyrotoxicosis have similar hemodynamic consequences with increased cardiac output and reduced systemic vascular resistance.

• 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.

Summary

Mass effect from a goiter is a serious complication with potentially life-threatening consequences. In rare instances, a goiter can compress nearby vessels, compromising cerebral blood flow, which can lead to an ischemic stroke. Ischemic strokes generally occur due to atherogenic or embolic phenomenon, albeit a rare etiology can be due to a mechanical obstruction of great vessels of the neck that provide blood supply to the brain. An unusual example of a similar obstruction is the mass effect of an expansive goiter on the carotid artery (CA) in the neck. We present a rare case of a 90-year-old female who had a historically untreated goiter for 13 years. She presented with symptoms of acute stroke, including right-sided weakness and dysarthria. CT angiogram of the neck revealed a massively enlarged thyroid gland causing compression and intermittent obstruction of the blood flow in the left common CA. Subsequently, the patient underwent a total thyroidectomy. Postoperatively, she had a remarkable recovery of her symptoms of right-sided weakness and dysarthria. Acknowledging stroke as a grave mechanical complication of a large multinodular goiter is crucial for timely and appropriate management to avoid serious consequences.

Learning points

• The natural history of euthyroid multinodular goiters include abnormal enlargement of the thyroid gland, which results in local compression of structures in the neck causing neurovascular injury.

• Timely diagnosis and surgical management of an enlarging goiter compressing the CA can reduce morbidity from an ischemic stroke.

• Ischemic stroke is a rare and dangerous complication of a giant multinodular goiter.

Summary

Increased intracranial pressure (ICP) can present with symptoms of headache, vomiting, visual changes, and tinnitus. Papilledema may be seen on physical exam. Thyroid disease has been a rare secondary cause of increased ICP. We present a 16-year-old female who had a worsening headache for 6 months. She was found to have signs, symptoms, physical exam findings, and diagnostic studies consistent with both increased ICP and previously undiagnosed Graves’ disease. The patient was treated with a 19-month course of methimazole 40 mg daily. Her headache and papilledema resolved shortly after medication initiation. The timeline of symptoms and resolution of her increased ICP symptoms with treatment of Graves’ disease suggests that hyperthyroidism was the underlying cause of her increased ICP. Clinicians should consider Graves’ disease as the etiology in pediatric patients presenting with signs and symptoms of increased ICP with papilledema.

Learning points

• Symptoms of increased intracranial pressure (ICP) include headache, vomiting, transient visual changes, and tinnitus.

• Secondary causes of increased ICP should be considered in males, young children, older patients, and those not overweight.

• Clinicians should consider Graves’ disease as the etiology in pediatric patients presenting with signs and symptoms of increased ICP with papilledema. They should assess for orbitopathy and thyromegaly and inquire about symptoms that would be indicative of hyperthyroidism.

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

• HNF1A mutations are a common cause of monogenic diabetes in patients presenting with early-onset diabetes and significant family history.

• Genetic testing in suspected patients allows for the identification of mutations causing monogenic diabetes.

• First-degree relatives of the affected individual should be considered for genetic testing.

• The use of sulfonylurea agents in patients with HNF1A-MODY can reduce dependence on insulin therapy and provide successful glycemic control.

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

• Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are usually well-tolerated, but some serious adverse effects have been documented.

• 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.

• Timely and close monitoring of the patient, with temporary discontinuation of this drug, may be recommended towards effective management.

• Studies demonstrating a comprehensive understanding of SGLT2i-related electrolyte derangements are warranted.

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.

Summary

Autonomous thyroid adenomas are caused by activating mutations in the genes encoding the thyroid-stimulating hormone receptor (TSHR) or mutations in the Gas subunit of the TSHR. Nodules with suspicious sonographic features should be submitted to fine-needle aspiration. Additional molecular testing may be performed to characterize the thyroid nodule’s malignant potential further. We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation after an ultrasound showed suspicious sonographic features and fine-needle aspiration was ‘suspicious for malignancy’. The patient underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma. Most reports of TSHR I568T mutation have been seen in patients with benign thyroid conditions. While there is insufficient data to suggest that the TSHR I568T mutation causes aggressive thyroid malignancy, we believe clinicians who identify the presence of this mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology.

Learning points

• Germline and somatic activating mutations in the genes coding for the thyroid-stimulating hormone receptor (TSHR) have been frequently reported in familial and sporadic autonomous thyroid adenomas and non-autoimmune hyperthyroidism.

• Most reports of TSHR I568T mutation have been detected in patients with benign thyroid conditions.

• We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation and subsequently underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma.

• Clinicians who identify the presence of TSHR I568T mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology.