Diagnosis of Resistance to Thyroid Hormone due to a Rare Mutation in the Thyroid Hormone Receptor Beta Gene in a Patient Previously Presumed to Have Graves' Disease.

Clinicians may confuse an impaired sensitivity to thyroid hormone with hyperthyroidism and offer an inappropriate treatment. We report a diagnosis of resistance to thyroid hormone (RTH) caused by a rare mutation in the thyroid hormone receptor beta gene in a patient previously presumed to have Graves' disease. We have found only one published case of a novel point mutation, c.749T>C (p.Ile250Thr variant) associated with 50% reduction in thyroid hormone receptor binding affinity for triiodothyronine in the I250T mutant; it was found in this patient. A 66-year-old male veteran, with a history of non-ischemic cardiomyopathy and arrhythmias, was referred by a cardiologist with concerns for a possible thyrotropin (TSH) adenoma on account of elevated TSH and free thyroxine (FT4) levels. Pituitary imaging was negative. He was previously treated with radioiodine for presumptive Graves' disease in the civilian sector. Examination revealed a goiter with no nodules. Repeat TSH and FT4 levels were elevated and also free triiodothyronine (FT3) and reverse triiodothyronine. These findings and other test results were consistent with RTH, which was confirmed by genetic testing. Mutation analysis showed the patient to be heterozygous for the p.Ile250Thr variant. He later developed hypothyroidism. Resistance to thyroid hormone can be misdiagnosed as hyperthyroidism with consequent inappropriate treatment. Treatment is not needed in most RTH-beta patients. Thyroid ablation should generally be avoided. Clinicians must be cautious whenever they encounter concurrent elevation of TSH, FT4, and FT3. This RTH-beta patient has a rare I250T mutant of the thyroid hormone receptor beta gene, the second reported case in the literature.

Diagnostic Evaluation of Hypoglycemia Due To an Insulinoma in a Deployed Infantryman: Significance of Neuroglycopenia and the Role of the Military Health System.

Insulinoma, the prototype of endogenous hyperinsulinemic hypoglycemia, is a very rare condition, with an incidence of four cases per million person-years. Its rate of occurrence in the U.S. military population is unknown. Two cases of insulinomas involving active duty service members have been published. However, there has been no reported case of an insulinoma in a deployed service member. We report the case of a 21-year-old infantryman with clinical hypoglycemia of insidious onset, manifesting with overt neuroglycopenic symptoms during his deployment as a combatant soldier, and the ultimate diagnosis of an insulinoma as the underlying cause. The series of multiple clinical evaluations and the unique circumstances leading to the formal evaluation of the patient's hypoglycemia and treatment are chronicled. The significance of neuroglycopenia and the diagnostic approach to any suspected case of hypoglycemia, the potential challenges and opportunities, and educational aspects of evaluation and management of the insulinoma are elaborated. The potential role of the Military Health System in facilitating the detection and treatment of this rare condition in the service member is discussed as well.

Chronic incretin-based therapy in cystic fibrosis-related diabetes: A tale of 3 patients treated with sitagliptin for over 5 years.

Cystic fibrosis-related diabetes (CFRD) affects 40-50% of adult patients with cystic fibrosis. Insulin therapy is recommended but there are therapeutic challenges, particularly risk of hypoglycemia and aversion of some patients to injectables. An oral incretin-based therapy using a DPP-4i (dipeptidyl peptidase-4 inhibitor), may be a reasonable option, especially in the early stage of the disease. The effect of chronic incretin-based therapy on CFRD is unknown. Here is a report of 3 cases of CFRD patients treated with sitagliptin and the response to therapy over a period of 5-10 years. An effective glycemic control was demonstrated in all the patients, at least during the first 5 years of sitagliptin treatment, and the benefit persisted for a decade in two of them. The secondary failure of the DPP-4i occurred in a CFRD patient with a phenotype resembling type 2 diabetes. A DPP-4i may have an important role in the management of CFRD.

Central Obesity in Africans: Anthropometric Assessment of Abdominal Adiposity and its Predictors in Urban Nigerians.

OBJECTIVE: To assess the occurrence of central obesity and identify its predictors in urban Africans using anthropometric tools. Another objective was to evaluate the anthropometric indices and their interaction with various cardiovascular risk factors. METHODS: In an obesity survey in a major Nigerian city, we measured the prevalence of central obesity in 998 randomly selected men and women using the IDF (International Diabetes Federation) criteria. Normalized values of three anthropometric indices, waist circumference (WC), WHR (waist-to-hip ratio) and WHtR (waist-to-height ratio) were also employed in assessing central adiposity and its predictors in the population. RESULTS: Most (61%) female participants had central obesity compared with 9% of the males based on the IDF waist criteria. Higher income level and physical inactivity were associated with central obesity (p < 0.001). In multivariate analyses, older participants and women were more likely to have central obesity (p < 0.001), but men had higher WHR than women at the same body mass index. WC was a stronger predictor of glucose intolerance than WHR, whereas WHR was more predictive of hypertension than WC. WHR showed a strong relationship with hypertension but not with glucose intolerance. WHtR was predictive of plasma glucose and diastolic blood pressure. WC showed strongest correlation with other indices. CONCLUSIONS: Central obesity was highly prevalent among women in this sample. It was associated with age, gender, socioeconomic status, physical inactivity, and it predicted glucose intolerance and hypertension. WC was a major determinant of both cardiovascular risk factors. It showed best correlation with other anthropometric indices.

Prevalence of diabetes and impaired glucose tolerance in Nigerians, Jamaicans and US blacks

The prevalence of type 2 diabetes, impaired glucose tolerance and associated risk factors were compared in sample surveys in Africa and the Caribbean with the Third National Health and Nutrition Survey (NHANES-III) from the United States. A total of 856 Nigerians, 1286 Jamaicans, and 1827 US blacks were included in the study. Body mass index (BMI) increased in a stepwise fashion across the three population groups, ie, 23 kg/m2 in Nigerians, 26 kg/m2 in Jamaicans, and 28 kg/m2 in US blacks. The persons aged 25-74, were 1 percent, 12 percent, 13 percent. Jamaican women were found to have the same prevalence of type 2 diabetes as US women (14 vs 13 percent, respectively); mean BMI was likewise very similar (28 kg/m2 in Jamaican and 29 kg/m2 in US women). BMI and waist-to-hip ratio were both associated with type 2 diabetes prevalence. Findings of this study confirm the marked gradient in type 2 diabetes risk among these genetically related populations and suggest that the blacks in the island nations of the Caribbean and the United States are at particularly high risk. Nigerians exhibited remarkably well-preserved glucose tolerance. Understanding the factors that limit the risk of type 2 diabetes in West Africa, beyond relative absence of obesity, would have considerable public health significance.(Au)