Certain HLA alleles are associated with stress-triggered Graves' disease and influence its course.

There are no studies on HLA analysis in patients in whom Graves' disease (GD) hyperthyroidism has been preceded by ≥1 stressful event. The aim of the present study was to identify predisposing or protecting HLA alleles and their effects on the course of GD in this subset of patients. We performed serological HLA typing in 58 Caucasian patients with stress-related GD and in 130 matched healthy controls (HC). We also performed genomic HLA typing in 20/58 patients and in all HC. Five HLA alleles and three loci were more frequent in patients compared to HC: B8, Cw7, C*07, C*17, DR3, DR4, DRB1*04, and DQ2. In contrast, B14 was less frequent in patients than in HC. Depending on outcome after ATD withdrawal (remission, exacerbation on-ATD, relapse off-ATD), in patients, some alleles/loci were over-represented, while others were under-represented. Age, FT3, and FT4 fold increase over the upper normal limit at onset were different depending on the allele/locus carried. In GD patients with stress-triggered hyperthyroidism, HLA typing may be helpful in predicting the outcome of the disease after ATD withdrawal.

Stress triggers the onset and the recurrences of hyperthyroidism in patients with Graves' disease.

The aim of this study was to evaluate the relationship of stressful events (SE) with the onset and outcome of Graves' disease (GD). Over a period of 21 years, we enrolled 58 consecutive patients in whom at least one SE had occurred ≤12 months before the onset of GD. Patients were treated with antithyroid drugs (ATD) for ≥12 months and followed up for ≥5 years after ATD withdrawal. We divided patients in three groups: REM (who reached remission; 25.9%); EXA (who experienced ≥1 exacerbation during ATD; 10.3%); and REL (who experienced ≥1 relapse after ATD withdrawal; 63.8%). The average age at onset was similar in the three groups. All males aged ≤25 years at GD onset relapsed at least once; no patient aged ≥51 years at GD onset relapsed ≥2 times. All patients who exacerbated or relapsed had at least one SE preceding each exacerbation or relapse. The time lag between SE and onset of GD (19.3±11.9 weeks) correlated with the age at onset (r=0.292, P=0.0002), particularly in the REL group (r=0.346, P=0.001). Overall, EXA and REL patients experienced more SE than REM patients (P=0.0002 and P=0.003, respectively). In the REL group, the overall number of SE was correlated with the number of relapses (r=0.486, P<0.0001). There exist GD patients who are prone to develop hyperthyroidism and its recurrences when exposed to SE. They are relatively young; the younger these patients are, the shorter is the time lag between SE and the onset of hyperthyroidism.

A patient with stress-related onset and exacerbations of Graves disease.

BACKGROUND: An 18-year-old, nonsmoking woman presented to her general practitioner with a 1-week history of weakness, fatigue, palpitations, nervousness, tremors, insomnia, heat intolerance, and sudden enlargement of a thyroid goiter that had been detected 2 years earlier. The patient's symptoms had started shortly after she experienced emotional stress. Diagnostic work-up disclosed an avid radioactive iodine uptake by the goiter. On ultrasound examination, the thyroid gland was enlarged with a diffusely hypoechogenic structure and intense vascularization. INVESTIGATIONS: Thyroid scintigraphy with (131)I; ultrasonography of the thyroid gland; and measurements of serum free T(3), free T(4), TSH levels and thyroid autoantibodies, including autoantibodies against thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb). DIAGNOSIS: Graves disease, with stress-related onset and subsequent stress-related exacerbations. MANAGEMENT: The patient was treated with methimazole to normalize levels of thyroid hormone and thyroid autoantibodies, and with bromazepam to help her cope with stress. The daily dose of methimazole was kept low during pregnancy. Over the 4 year period when the patient was taking methimazole, exacerbations of hyperthyroidism occurred twice: during her first pregnancy and 9 months after her first delivery. On all three occasions, symptoms were preceded by stressful life events. Further exacerbations were avoided by starting bromazepam treatment soon after the patient experienced stressful events.

Altered intestinal absorption of L-thyroxine caused by coffee.

OBJECTIVE: To report eight case histories, and in vivo and in vitro studies showing coffee's potential to impair thyroxine (T4) intestinal absorption. DESIGN: Of eight women with inappropriately high or nonsuppressed thyroid-stimulating hormone (TSH) when T4 was swallowed with coffee/espresso, six consented to the evaluation of their T4 intestinal absorption. This in vivo test was also administered to nine volunteers. In three separate tests, two 100 microg T4 tablets were swallowed with coffee, water, or water followed, 60 minutes later, by coffee. Serum T4 was assayed over the 4-hour period of the test. Two patients and two volunteers also agreed on having tested the intestinal absorption of T4 swallowed with solubilized dietary fibers. In the in vitro studies, classical recovery tests on known concentrations of T4 were performed in the presence of saline, coffee, or known T4 sequestrants (dietary fibers, aluminium hydroxide, and sucralfate). MAIN OUTCOME: For the in vivo test, average and peak incremental rise of serum T4 (AIRST4 and PIRST4), time of maximal incremental rise of serum T4 (TMIRST4), and area under the curve (AUC) were determined. In patients and volunteers, the four outcome measures were similar in the water and water + coffee tests. In patients and volunteers, compared to water, coffee lowered AIRST4 (by 36% and 29%), PIRST4 (by 30% and 19%), and AUC (by 36% and 27%) and delayed TMIRST4 (by 38 and 43 minutes); bran was a superior interferer. In the in vitro studies, coffee was weaker than known T4 sequestrants. CONCLUSION: Coffee should be added to the list of interferers of T4 intestinal absorption, and T4 to the list of compounds whose absorption is affected by coffee.

Germline mutation of von Hippel-Lindau (VHL) gene 695 G>A (R161Q) in a patient with a peculiar phenotype with type 2C VHL syndrome.

Von Hippel-Lindau (VHL) disease is an autosomal dominant familial neoplastic disorder with an estimated birth incidence of approximately 1:36000 live. VHL has intrafamilial variability expression and it is characterized by the predisposition to develop hemangioblastomas of the central nervous system and retina, pheochromocytomas, clear-cell renal carcinoma, adenomas, and carcinomas of the pancreas, paragangliomas, renal and pancreatic cysts, papillary cystadenomas of the epididymis and, rarely, cystadenomas of the endolymphatic sac tumor and broad ligament. We describe a Sicilian girl with type 2C VHL who showed the apparently de novo mutation R161Q in association with an extra-axial supratentorial frontal meningioma, which can be included as a characteristic sign in VHL.