Search for other papers by Tejal Patel in
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Search for other papers by Rachel Longendyke in
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Department of Pediatrics, George Washington School of Medicine, Washington, District of Columbia, USA
Search for other papers by Roopa Kanakatti Shankar in
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Search for other papers by Nadia Merchant in
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Summary
Iodine nutrition is a growing issue within the USA due to newer trends of non-iodized salts. There are no recent reviews looking at the current state of iodine deficiency-induced hypothyroidism in children in the USA. We performed a retrospective chart review at our tertiary pediatric endocrine clinic; four met the diagnostic criteria for iodine deficiency defined by a low urine iodine level. We further characterized severity of disease, risk factors, goiter, thyroid labs and antibodies. All cases had significant goiter and were diagnosed within the last 2 years. One case had iodine deficiency due to no iodized salt intake along with concurrent diagnosis of developmental delay and multiple food allergies, while others involved the use of non-iodized salts. Two cases had iodine deficiency along with autoimmunity. It is critical to obtain a dietary history for all patients who present with goiter and/or hypothyroidism. There may be a need to consider reevaluating current preventative measures for iodine deficiency, especially for certain vulnerable populations such as children who do not consume iodized salt.
Learning points
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In recent decades, iodine nutrition has become a growing concern due to changing dietary patterns and food manufacturing practices.
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A dietary history is crucial to obtain in children presenting with hypothyroidism and goiter, especially in children with restrictive diets due to behavioral concerns, developmental delays, or multiple food allergies.
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Of the 12 different types of salts commercially available, only table salt contains iodine in an appropriate amount; thus, individuals using specialty salts can develop mild to moderate iodine deficiency-related thyroid disease.
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Search for other papers by Ahmed Torky in
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Summary
Neonatal hypoglycemia is a serious condition that can have a major impact on the growing neonatal brain. The differential diagnosis of neonatal hypoglycemia is broad and includes hyperinsulinism as well as panhypopituitarism. The FOXA2 gene has been involved in the development of the pancreas as well as the pituitary gland. Six cases have been reported thus far with FOXA2 mutations presenting with variable degrees of hypopituitarism, and only two patients had permanent hyperinsulinism; other cases have been reported with microdeletions in 20p11, the location that encompasses FOXA2, and those patients presented with a wider phenotype. A full-term female infant presented with severe hypoglycemia. Critical sampling showed an insulin of 1 mIU/mL, suppressed beta-hydroxybutyric acids, and suppressed free fatty acids. Blood glucose responded to glucagon administration. Growth hormone (GH) stimulation test later showed undetectable GH in all samples, and cortisol failed to respond appropriately to stimulation. Gonadotropins were undetectable at 1 month of life, and MRI showed ectopic posterior pituitary, interrupted stalk, hypoplastic anterior pituitary, cavum septum pellucidum, and diminutive appearance of optic nerves. Whole-exome sequencing revealed a likely pathogenic de novo c.604 T>C, p.Tyr202His FOXA2 mutation. We expand the known phenotype on FOXA2 mutations and report a likely pathogenic, novel mutation associated with hyperinsulinism and panhypopituitarism.
Learning points
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FOXA2 has been shown to play an important role in the neuroectodermal and endodermal development.
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FOXA2 mutation may lead to the rare combination of hyperinsulinism and panhypopituitarism.
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Patients reported so far all responded well to diazoxide. Dysmorphology may be subtle, and liver functions should be monitored.
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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
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Human T-cell lymphotropic virus-1 infection and adult T-cell leukemia and lymphoma are associated with high rates of hypercalcemia and hypercalcemic crises.
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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.
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Hypercalcemia in such settings is highly responsive to monoclonal antibodies against RANKL given the role the ligand plays in resorptive hypercalcemia.
Search for other papers by Susan Ahern in
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Summary
In this case report, we present a novel mutation in Lim-homeodomain (LIM-HD) transcription factor, LHX3, manifesting as combined pituitary hormone deficiency (CPHD). This female patient was originally diagnosed in Egypt during infancy with Diamond Blackfan Anemia (DBA) requiring several blood transfusions. Around 10 months of age, she was diagnosed and treated for central hypothyroidism. It was not until she came to the United States around two-and-a-half years of age that she was diagnosed and treated for growth hormone deficiency. Her response to growth hormone replacement on linear growth and muscle tone were impressive. She still suffers from severe global development delay likely due to delay in treatment of congenital central hypothyroidism followed by poor access to reliable thyroid medications. Her diagnosis of DBA was not confirmed after genetic testing in the United States and her hemoglobin normalized with hormone replacement therapies. We will review the patient’s clinical course as well as a review of LHX3 mutations and the associated phenotype.
Learning points:
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Describe an unusual presentation of undertreated pituitary hormone deficiencies in early life
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Combined pituitary hormone deficiency due to a novel mutation in pituitary transcription factor, LHX3
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Describe the clinical phenotype of combined pituitary hormone deficiency due to LHX3 mutations
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Summary
Central pontine myelinolysis (CPM) usually occurs with rapid correction of severe chronic hyponatremia. Despite the pronounced fluctuations in serum osmolality, CPM is rarely seen in diabetics. This is a case report of CPM associated with hyperglycemia. A 45-year-old non-smoking and non-alcoholic African American male with past medical history of type 2 diabetes, hypertension, stage V chronic kidney disease and hypothyroidism presented with a two-week history of intermittent episodes of gait imbalance, slurred speech and inappropriate laughter. Physical examination including complete neurological assessment and fundoscopic examination were unremarkable. Laboratory evaluation was significant for serum sodium: 140 mmol/L, potassium: 3.9 mmol/L, serum glucose: 178 mg/dL and serum osmolality: 317 mosmol/kg. His ambulatory blood sugars fluctuated between 100 and 600 mg/dL in the six weeks prior to presentation, without any significant or rapid changes in his corrected serum sodium or other electrolyte levels. MRI brain demonstrated a symmetric lesion in the central pons with increased signal intensity on T2- and diffusion-weighted images. After neurological consultation and MRI confirmation, the patient was diagnosed with CPM secondary to hyperosmolar hyperglycemia. Eight-week follow-up with neurology was notable for near-complete resolution of symptoms. This case report highlights the importance of adequate blood glucose control in diabetics. Physicians should be aware of complications like CPM, which can present atypically in diabetics and is only diagnosed in the presence of a high index of clinical suspicion.
Learning points:
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Despite the pronounced fluctuations in serum osmolality, central pontine myelinolysis (CPM) is rarely seen in diabetics. This case report of CPM associated with hyperglycemia highlights the importance of adequate blood glucose control in diabetics.
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Physicians should be aware of complications like CPM in diabetics.
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CPM can present atypically in diabetics and is only diagnosed in the presence of a high index of clinical suspicion.
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Anderson Cancer Institute, Memorial University Medical Center, Savannah, Georgia, 31404, USA
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Summary
Lipoid congenital adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is most commonly caused by mutations in steroidogenic acute regulatory protein (STAR), which is required for the movement of cholesterol from the outer to the inner mitochondrial membranes to synthesize pregnenolone. This study was performed to evaluate whether the salt-losing crisis and the adrenal inactivity experienced by a Scandinavian infant is due to a de novo STAR mutation. The study was conducted at the University of North Dakota, the Mercer University School of Medicine and the Memorial University Medical Center to identify the cause of this disease. The patient was admitted to a pediatric endocrinologist at the Sanford Health Center for salt-losing crisis and possible adrenal failure. Lipoid CAH is an autosomal recessive disease, we identified two de novo heterozygous mutations (STAR c.444C>A (STAR p.N148K) and STAR c.557C>T (STAR p.R193X)) in the STAR gene, causing lipoid CAH. New onset lipoid CAH can occur through de novo mutations and is not restricted to any specific region of the world. This Scandinavian family was of Norwegian descent and had lipoid CAH due to a mutation in S TAR exons 4 and 5. Overexpression of the STAR p.N148K mutant in nonsteroidogenic COS-1 cells supplemented with an electron transport system showed activity similar to the background level, which was ∼10% of that observed with wild-type (WT) STAR. Protein-folding analysis showed that the finger printing of the STAR p.N148K mutant is also different from the WT protein. Inherited STAR mutations may be more prevalent in some geographical areas but not necessarily restricted to those regions.
Learning points
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STAR mutations cause lipoid CAH.
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This is a pure population from a caucasian family.
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Mutation ablated STAR activity.
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The mutation resulted in loosely folded conformation of STAR.
