Abnormal thyroid function: an unusual presentation of pituitary stalk interruption syndrome.

Summary: An 11-year-old girl with past medical history of septic shock and multi-organ failure at age 5 presented to her primary care doctor with concern for pallor of the lips. Laboratory studies demonstrated low free thyroxine (T4) and normal thyroid-stimulating hormone (TSH). A referral to endocrinology was made where the patient was evaluated, and laboratory evaluation was repeated. The patient was asymptomatic and clinically euthyroid with a height consistent with her mid-parental height and was in mid- to late-puberty. The repeated laboratory evaluation demonstrated a pattern suggestive of primary hypothyroidism with low free T4 and an elevated TSH. However, the magnitude of elevation of TSH was less than expected, given the degree of lowering of free T4; therefore, central hypothyroidism was considered. Workup was initiated, and laboratory studies and MRI imaging confirmed an underlying diagnosis of panhypopituitarism in the setting of pituitary stalk interruption syndrome. Learning points: Pituitary stalk interruption syndrome is a rare but important cause of panhypopituitarism. Central hypothyroidism should be suspected in patients with low free thyroxine with an inappropriate degree of elevation of thyroid-stimulating hormone. Workup of central hypothyroidism should include multi-pituitary hormone assessment, and, if evident, MRI imaging should be done. Adrenal insufficiency should be suspected in a hypotensive, critically ill patient who is failing to improve on standard-of-care therapy.

Acute metabolic responses to high fructose corn syrup ingestion in adolescents with overweight/obesity and diabetes.

INTRODUCTION: Childhood obesity remains high in prevalence. Sugar-sweetened beverages containing high fructose corn syrup (HFCS) are a common source of excess calories among children and adolescents. Fructose metabolism differs from glucose metabolism, which may also differ from fructose + glucose metabolism in HFCS consumption. The purpose of this study was to determine the acute metabolic effects of HFCS ingestion after soft drink consumption in adolescents who are lean, have overweight/obesity, or have type 2 diabetes (T2DM). METHODS: Adolescents age 13-19 years were recruited into three groups: lean controls (n = 10), overweight/ obese without diabetes (n = 10), or uncomplicated T2DM on metformin monotherapy (n = 5). After an overnight fast, subjects drank 12 ounces of soda containing HFCS. Blood samples were collected at time zero and every 15 min for 120 min to be analyzed for fructose, glucose, and insulin levels. RESULTS: Glucose and fructose concentrations rose quickly in the first 15 min. Fructose, which was very low at baseline, rose to 100-200 µM and remained higher than fasting concentrations even at 120 min in all groups. Glucose increased after soft drink consumption, with the highest concentrations among subjects with T2DM, but returned to baseline fasting levels at 120 min. Insulin levels increased 15 min after soft drink consumption and were the highest in the obese group. Lactate rose non-significantly in all subjects, with no differences between groups. CONCLUSION: Among adolescents who are lean, overweight/obese, or have T2DM, drinking an HFCS-containing soft drink exposes the liver to fructose. Glucose excursions in T2DM may be impacted by exaggerated glucose cycling, or fructose metabolism to glucose. The context of fructose consumption with or without other carbohydrates is an important consideration in studies of fructose metabolism.

Stearoyl-CoA desaturase enzyme 1 inhibition reduces glucose utilization for de novo fatty acid synthesis and cell proliferation in 3T3-L1 adipocytes.

Stearoyl-CoA desaturase enzyme 1 (SCD1) is a lipogenic enzyme that is upregulated in obesity, insulin resistance, and cancer. Since glucose is a substrate for both de novo fatty acid synthesis and deoxyribose synthesis, we hypothesized that SCD1 affects these multiple synthetic pathways through changes in glucose utilization. This study determined glucose utilization for fatty acid synthesis and cell proliferation in 3T3-L1 preadipocytes during SCD1 inhibition. The effects of SCD1 on cellular metabolism as mediated by its monounstaurated fatty acid products (palmitoleate and oleate) were also observed. 3T3-L1 preadipocytes underwent differentiation induction in conjunction with one of the following treatments for 4 days: (A) no treatment, (B) SCD1 inhibitor CGX0290, (C) CGX0290 + palmitoleate, or (D) CGX0290 + oleate. All cells received medium with 50 % [U13C]-glucose. Cells were harvested on day 7 for studies of fatty acid metabolism, tricarboxylic acid (TCA) cycle activities, and deoxyribose synthesis. CGX0290 decreased fatty acid desaturation, glucose utilization for fatty acid synthesis (acetyl-CoA enrichment), and de novo synthesis. CGX0290 treatment also led to decreased cell density through increased cell death. Further analysis showed that deoxyribose new synthesis and oxidative pentose phosphate pathway activity were unchanged, while non-oxidative transketolase pathway activity was stimulated. Palmitoleate and oleate supplementation each partially ameliorated the effects of CGX0290. In 3T3-L1 cells, SCD1 promotes glucose utilization for fatty acid synthesis. In cell proliferation, SCD1 may promote cell survival, but does not impact the oxidative pathway of deoxyribose production. These effects may be mediated through the production of palmitoleate and oleate.

Hyperinsulinism presenting in childhood and treatment by conservative pancreatectomy.

OBJECTIVE: To describe the uncommon presentation of hyperinsulinism in an 8-year-old boy. METHODS: We describe the patient's clinical findings, results from biochemical and imaging studies, surgical approach, and outcome. The discussion encompasses a review of literature that provided the basis for the diagnostic and surgical approach applied to this patient's case. RESULTS: An obese 8.5-year-old boy initially presented with hypoglycemic seizures after initiation of dietary changes to treat obesity. Biochemical analysis indicated hyperinsulinism. Endoscopic ultrasonography showed no pancreatic lesions suggestive of insulinoma. Genetic studies identified no known mutations in the ABCC8, KCNJ11, GCK, or GLUD1 genes. Selective arterial calcium stimulation and hepatic venous sampling did not document a focal source for hyperinsulinism in the pancreas, and positron emission tomography with 18-fluoro-L-3,4-dihydroxyphenylalanine showed diffusely increased uptake in the pancreas. The patient ultimately required partial pancreatectomy because of continued hypoglycemia while taking diazoxide and octreotide. Intraoperative glucose monitoring directed the extent of surgical resection. A 45% pancreatectomy was performed, which resolved the hypoglycemia but led to impaired glucose tolerance after surgery. CONCLUSION: The unusual presentation of hyperinsulinism in childhood required a personalized approach to diagnosis and surgical management using intraoperative glucose monitoring that resulted in a conservative pancreatectomy.

Measurement of glucose and fructose in clinical samples using gas chromatography/mass spectrometry.

OBJECTIVE: The impact of increased fructose consumption on carbohydrate metabolism is a topic of current interest, but determination of serum level has been hindered due to low concentration and interference from serum glucose. We are reporting a method for the quantification of glucose and fructose in clinical samples using gas chromatography/mass spectrometry (GC/MS). The accuracy and precision of GC/MS and an enzymatic assay were compared. DESIGN AND METHODS: Mass spectrometry fragmentation patterns of methyloxime peracetate derivatized aldose and ketose were determined. Unique fragments for glucose and fructose were used for quantitative analysis using isotope labeled recovery standards. RESULTS: Methyloxime peracetate derivatives of glucose and fructose showed characteristic loss of acetate (M-60) or ketene (M-42) under chemical ionization (CI). Under electron impact (EI) ionization, a unique C1-C2 fragment of glucose was formed, while a C1-C3 fragment was formed from keto-hexoses. These unique fragments were used in the quantitative assay of glucose and fructose in clinical samples. In clinical samples, the GC/MS assay has a lower limit of detection than that of the enzymatic assay. In plasma samples from patients evaluated for diabetes the average serum glucose and fructose were 6.19+/-2.72 mM and 46+/- 25.22 microM. Fructose concentrations in many of these samples were below the limit of detection of the enzymatic method. CONCLUSION: Derivatization of aldose and ketose monosaccharides to their respective O-methyloxime acetates for GC/MS analysis is a facile method for determination of serum/plasma glucose and fructose samples.