Thursday, April 28, 2011

More on last article: Additional autoimmune disease found in one-third of patients with type 1 diabetes

At diagnosis of type 1 diabetes, approximately 33% of patients are positive for at least one additional organ-specific autoantibody, according to new data.

Researchers at the Barbara Davis Center for Childhood Diabetes assessed 491 children diagnosed with type 1 diabetes from 2004 to 2009 for other autoimmune conditions. They measured thyroid peroxidase autoantibodies (TPOAb) to screen for autoimmune thyroid disease, tissue transglutaminase autoantibodies (TTGAb) for celiac disease and 21-hydroxylase autoantibodies (21OHAb) for Addison’s disease.

“We sought to define the prevalence of nonislet, organ-specific autoantibodies at the diagnosis of type 1 diabetes and to determine the prevalence of comorbid autoimmune diseases,” the researchers wrote.

Of the 491 children, 82.7% were white and 53.4% were boys. At the time of diagnosis with type 1 diabetes, mean age was 9.6 years and the average HbA1c level was 11.6%.

Measurements of TPOAb, TTGAb and 21OHAb were collected within 16 days, on average, and patients were diagnosed with autoimmune thyroid disease, celiac disease or Addison’s disease within 45 days.

Overall, 32.6% of the children had at least one nonislet, organ-specific autoantibody. Of these, 18.6% were diagnosed with additional autoimmune disease. Results revealed that 24.8% were positive for TPOAb, of whom 12.3% had autoimmune thyroid disease. Of the 11.6% with TTGAb, 24.6% had celiac disease. Just 1% of children had 21OHAb, and the researchers found only one case of Addison’s disease.

“Ongoing follow-up of this cohort will be important to determine the natural history of organ-specific autoimmunity in patients with type 1 diabetes,” the researchers wrote. “Key questions remain, including the incidence of autoantibodies over time, the evolution from positive antibodies to disease, the genetic influences on autoimmunity and disease, and patient characteristics that may influence antibody or disease development.”

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Disclosure: The researchers report no relevant financial disclosures.

Thursday, April 28, 2011

Type 1 Diabetes, Celiac or Addison’s?

After noticing a growing trend in children diagnosed with Type 1 Diabetes, doctors and medical researchers have announced a new study measuring the correlation between this autoimmune disorder as well as three others. Addison’s disease, celiac disease, and autoimmune thyroid disease often have antibodies present in children at the same time that they are diagnosed with Type 1 Diabetes.

It has recently been reported that fifteen to thirty percent of people with Type 1 diabetes have also been diagnosed, and about 4 to 9 percent have been diagnosed with celiac disease. Addison’s disease is at the bottom of the list with less than one percent being diagnosed. Children who have been confirmed to have diabetes should be tested yearly for an autoimmune thyroid disease, and for celiac disease if other symptoms become apparent. There is no real screening schedule for Addison’s disease.


Wednesday, April 27, 2011

Gastric inhibitory polypeptide-dependent cortisol hypersecretion

André Lacroix, M.D., Edouard Bolté, M.D., Johanne Tremblay, Ph.D., John Dupré, M.D., Pierre Poitras, M.D., Hélène Fournier, M.D., Jean Garon, M.D., Dominique Garrel, M.D., Francis Bayard, M.D., Ph.D., Raymond Taillefer, M.D., Richard J. Flanagan, Ph.D., and Pavel Hamet, M.D., Ph.D.
N Engl J Med 1992; 327:974-980October 1, 1992


Corticotropin-independent nodular adrenal hyperplasia is a rare cause of Cushing's syndrome, and the factors responsible for the adrenal hyperplasia are not known.


We studied a 48-year-old woman with Cushing's syndrome, nodular adrenal hyperplasia, and undetectable plasma corticotropin concentrations in whom food stimulated cortisol secretion.


Cortisol secretion had an inverse diurnal rhythm in this patient, with low-to-normal fasting plasma cortisol concentrations and elevated postprandial cortisol concentrations that could not be suppressed with dexamethasone. The cortisol concentrations increased in response to oral glucose (4-fold increase) and a lipid-rich meal (4.8-fold increase) or a protein-rich meal (2.6-fold increase), but not intravenous glucose. The infusion of somatostatin blunted the plasma cortisol response to oral glucose. Intravenous infusion of gastric inhibitory polypeptide (GIP) for one hour increased the plasma cortisol concentration in the patient but not in four normal subjects. Fasting plasma GIP concentrations in the patient were similar to those in the normal subjects; feeding the patient test meals induced increases in plasma GIP concentrations that paralleled those in plasma cortisol concentrations. Cell suspensions of adrenal tissue from the patient produced more cortisol when stimulated by GIP than when stimulated by corticotropin. In contrast, adrenal cells from normal adults and fetuses or patients with cortisol-producing or aldosterone-producing adenomas responded to corticotropin but not to GIP.


Nodular adrenal hyperplasia and Cushing's syndrome may be food-dependent as a result of abnormal responsiveness of adrenal cells to physiologic secretion of GIP. "Illicit" (ectopic) expression of GIP receptors on adrenal cells presumably underlies this disorder. (N Engl J Med 1992;327:974–80.)

Media in This Article

Figure 1Plasma Cortisol Concentrations in a Patient with Food-Induced Cushing's Syndrome during Fasting and after Eating.
Figure 2Plasma Cortisol and GIP Responses to Oral Glucose Administration (○), Intravenous Glucose Administration (●), and Protein-Rich (□) and Lipid-Rich () Meals in a Patient with Food-Induced

Saturday, April 09, 2011

Presentation of Primary Adrenal Insufficiency in Childhood

Susan Hsieh and Perrin C. White

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390

Address all correspondence and requests for reprints to: Perrin C. White, M.D., University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9063. E-mail:

Context: Primary adrenal insufficiency is usually diagnosed in infancy or adulthood, and cases presenting in childhood have not been systematically reviewed.

Objective: Our objective was to determine etiologies, signs, and symptoms of primary adrenal insufficiency presenting in childhood.

Design and Setting: We conducted a retrospective chart review at a tertiary-care pediatric hospital.

Patients: Patients were children with corticoadrenal insufficiency, glucocorticoid deficiency, or mineralocorticoid deficiency.

Results: Seventy-seven cases were identified in 1999–2010. Thirty-five had congenital adrenal hyperplasia (CAH) and were not reviewed further. Forty-two patients (20 diagnosed at our institution) had primary adrenal insufficiency. These had etiologies as follows: autoimmune (18), autoimmune polyendocrinopathy syndrome (an additional five), ACTH resistance (four), adrenoleukodystrophy (three), adrenal hypoplasia congenita (two), adrenal hemorrhage (two), IMAGe syndrome (one), and idiopathic (two). Of 20 patients diagnosed at our institution, two were being monitored when adrenal insufficiency developed and were not included in the analysis of presenting signs and symptoms: 13 of 18 patients were hypotensive; 12 of 18 had documented hyperpigmentation. Hyponatremia (<135 mEq/liter) occurred in 16 of 18. However, hyperkalemia (>5.0 mEq/liter) was noted in only nine. Hypoglycemia and ketosis were documented in four of 15 and four of six patients in whom it was sought, respectively. Fifteen patients underwent cosyntropin stimulation testing with median baseline and stimulated cortisol of 1.1 and 1.2 µg/dl, respectively. ACTH and renin were markedly elevated in all patients.

Conclusions: Hyperkalemia is not a consistent presenting sign of primary adrenal insufficiency in childhood, and its absence cannot rule out this condition. A combination of chronic or subacute clinical symptoms, hypotension, and hyponatremia should raise suspicion of adrenal insufficiency.