Impact of Lifestyle Changes During Ramadan on Thyroid Function Tests in Hypothyroid Patients Taking Levothyroxine.

OBJECTIVE: The holy month of Ramadan poses a challenge for levothyroxine-treated patients due to altered eating habits and time restrictions. The aim of this study was to examine the impact of lifestyle changes during Ramadan on thyroid function tests in hypothyroid patients taking levothyroxine in the United Arab Emirates. METHODS: Retrospective design whereby levothyroxine-treated hypothyroid patients who had thyroid function tests within 3 months pre-Ramadan and within 2 months post-Ramadan were included. We looked at adherence to levothyroxine, eating pattern, and levothyroxine administration in relation to meal times during Ramadan. Pre- and post-Ramadan thyroid function tests and the potential impact of independent variables using a random-intercept mixed effects linear model were examined. RESULTS: A total of 112 patients (89 females) were recruited in the study, with a mean age ± standard error (SE) of 44.70±1.36 years (range, 19.0 to 79.0 years). The mean thyroid-stimulating hormone (TSH) within 3 months before Ramadan was 1.809±0.094 mIU/L (median, 41.5 days; interquartile range [IQR], 25.0 to 73.0 days), while the mean TSH within 2 months post-Ramadan was higher at 3.072±0.312 mIU/L (median, 27.5 days; IQR, 14.0 to 42.0 days). Post-Ramadan, 36 out of 112 patients had a plasma TSH outside of the normal reference range. The independent variable outcomes model showed that older patients and males were more likely to have an increased plasma TSH post-Ramadan. There was no relationship between the time of levothyroxine administration and change in TSH level. CONCLUSION: Levothyroxine-treated hypothyroid patients showed a significant increase in plasma TSH post-Ramadan, amounting to 2.525 standard deviations, with older patients and males more likely to be affected. ABBREVIATIONS: IQR = interquartile range; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Levothyroxine Administration during Ramadan: A Prospective Randomized Controlled Trial.

BACKGROUND AND AIM: We have previously shown in a retrospective analysis that the plasma thyroid-stimulating hormone (TSH) rises significantly post-Ramadan in levothyroxine-treated hypothyroid patients, possibly as a result of lifestyle alterations and time restrictions during the nonfasting period from dusk until dawn. The aim of this study is to determine the best time to instruct patients to take levothyroxine during Ramadan so as to minimize changes in thyroid function tests during this period. METHODS: In a randomized prospective design, hypothyroid patients taking levothyroxine were randomized to receive instructions to take levothyroxine at one of the following 3 times during Ramadan: (group 1) at dusk 30-min before Iftar meal, (group 2) 3 or more hours after Iftar meal, or (group 3) at dawn 30-min before Suhur meal. Thyroid function tests were performed within 3 months before Ramadan and within 6 weeks post-Ramadan. Data from patients with at least 1 blood test before or after Ramadan were analyzed using mixed-effects regression models. RESULTS: Plasma TSH levels were available at one or more time points for 148 patients, group 1 (n = 50), group 2 (n = 46), and group 3 (n = 52). A statistically significant within-patient increase in plasma TSH was seen in patients at the 25th percentile pre-Ramadan in groups 2 and 3 (p values <0.001), but not in group 1. A statistically significant within-patient decrease in plasma TSH was found in patients at the 75th percentile in group 1 only. For patients at the 50th percentile pre-Ramadan, no statically significant within-patient changes were found, though descriptively, increases in plasma TSH were observed for groups 2 and 3, while a decrease was observed in group 1. CONCLUSIONS: Our data suggest that instructing patients to take levothyroxine at the time of breaking the fast 30 min before the Iftar meal minimizes unfavorable changes in plasma TSH post-Ramadan. In contrast, instructing patients to take levothyroxine 3 h post-Iftar or 30 min before Suhur led to a greater rise in post-Ramadan TSH.

Association between radioiodine therapy for Graves' hyperthyroidism and thyroid-associated ophthalmopathy.

To investigate the role of radioactive iodine (RAI) in the onset and progression of thyroid-associated ophthalmopathy (TAO). Forty-six Graves' disease patients with mild or no ophthalmopathy were prospectively treated with carbimazole (CBZ) (n = 22) or RAI (n = 24). Treatment effects were evaluated clinically over 12 months, and with orbital MRI-measured extra-ocular muscle (EOM) volumes at baseline and at 6 months. The diagnosis of TAO was based on the clinical activity score (CAS) system. There were 11/22 CBZ and 10/24 RAI patients with active ophthalmopathy at baseline. Despite greater mean TSH levels post-RAI (P = 0.003), there was no increase in the likelihood of developing active ophthalmopathy (OR 0.95; 95% CI 0.56-1.61, P = 0.9) or EOM dysfunction (OR 0.52; 95% CI 0.26-1.06, P = 0.074). The increased mean palpebral aperture post-RAI (P = 0.023) and greater mean proptosis in the CBZ group (P = 0.005) were not confirmed when the absolute values of these measurements were examined. There was no association between the treatment received and MRI-measured EOM volumes. In this study, RAI therapy for Graves' disease did not increase the risk of progression or development of ophthalmopathy in patients with mild or no eye disease at baseline.

Unusual Combination of MEN-1 and the Contiguous Gene Deletion Syndrome of CAH and Ehlers-Danlos Syndrome (CAH-X).

The contiguous gene deletion syndrome of congenital adrenal hyperplasia and Ehlers-Danlos syndrome, named CAH-X, is a rare entity that occurs because of a deletion of a chromosomal area containing 2 neighboring genes, TNXB and CYP21A. Here, we describe a patient from a consanguineous family in which coincidentally MEN-1 syndrome is associated with CAH-X, causing particular challenges explaining the phenotypic features of the patient. A 33-year-old man with salt-wasting congenital adrenal hyperplasia and classic-like Ehlers-Danlos syndrome presented with an adrenal crisis with a history of recurrent hypoglycemia, abdominal pain, and vomiting. He was found to have primary hyperparathyroidism, hyperprolactinemia, and pancreatic neuroendocrine tumors, as well as primary hypogonadism, large adrenal myelolipomas, and low bone mineral density. A bladder diverticulum was incidentally found. Genetic analysis revealed a heterozygous previously well-described MEN1 mutation (c.784-9G > A), a homozygous complete deletion of CYP21A2 (c.1-?_1488+? del), as well as a large deletion of the neighboring TNXB gene (c.11381-?_11524+?). The deletion includes the complete CYP21A2 gene and exons 35 through 44 of the TNXB gene. CGH array found 12% homozygosity over the whole genome. This rare case illustrates a complex clinical scenario with some initial diagnostic challenges.

Acute delirium in the setting of primary hypothyroidism: the role of thyroid hormone replacement therapy.

Psychiatric illness, mostly mania and psychosis, are reported to occur after rapid normalization of thyroid function in patients with primary hypothyroidism. It is generally believed that the gradual restoration of thyroid function may reduce the risk of psychiatric complications. This case report describes the occurrence of acute delirium in a 67-year-old man with primary hypothyroidism shortly after the initiation of thyroid hormone replacement. The use of low-dose thyroxine initially and persistent severe biochemical hypothyroidism on presentation with psychiatric symptoms illustrate that psychiatric illness can still occur despite unaggressive thyroid hormone replacement. A temporal relationship with the initiation of thyroxine and rapid recovery of mental state over 1 to 2 weeks differentiate this condition from hypothyroidism-related psychopathology, which tends to have a more prolonged course.

Stress and thyroid autoimmunity.

While many studies have shown a connection between stress and autoimmune disease, most of the evidence for stress contributing to the onset and course of autoimmune disease is circumstantial and the mechanisms by which stress affects autoimmune disease are not fully understood. The best circumstantial evidence for an effect of stress on autoimmune thyroid disease is the well-known relationship between the onset of Graves' hyperthyroidism and major stress but even this is debated. However, most of the recent case-control studies have supported stress as a factor that affects the onset and clinical course of Graves' disease. On the other hand, there have been few reports concerning the possible relationship between stress and Hashimoto's thyroiditis. Because the onset and course of Hashimoto's thyroiditis is generally insidious, the effect of stress on Hashimoto's thyroiditis might be overlooked. Numerous human and animal studies have demonstrated that psychological and physiologic stressors induce various immunologic changes. Stress affects the immune system either directly or indirectly through the nervous and endocrine systems. These immune modulations may contribute to the development of autoimmunity as well as the susceptibility to autoimmune disease in genetically predisposed individuals. Stress can be one of the environmental factors for thyroid autoimmunity.

Targeting the thyrotropin receptor in thyroid disease.

INTRODUCTION: The thyrotropin receptor (TSHR) is essential for thyroid growth and for the production of thyroid hormones. It is unique among the glycoprotein hormone receptors, in that some of the TSHRs undergo cleavage and shedding of the alpha subunit. AREAS COVERED: This review discusses the structure and function of the TSHR, followed by an evaluation of its role in thyroid disease. Possible limitations of the TSHR as a therapeutic target are also discussed. EXPERT OPINION: The TSHR is involved in a number of hereditary and acquired disorders of the thyroid making it of potential importance as a therapeutic target in thyroid disease. Expression of the TSHR in several non-thyroidal tissues and the development of systemic manifestations of thyroid disease suggest that the TSHR is also of interest as a therapeutic target outside the thyroid.

Determinants of extraocular muscle volume in patients with graves' disease.

Background. To examine factors contributing to extraocular muscle (EOM) volume enlargement in patients with Graves' hyperthyroidism. Methods. EOM volumes were measured with orbital magnetic resonance imaging (MRI) in 39 patients with recently diagnosed Graves' disease, and compared to EOM volumes of 13 normal volunteers. Thyroid function tests, uptake on thyroid scintigraphy, anti-TSH-receptor antibody positivity and other parameters were then evaluated in patients with EOM enlargement. Results. 31/39 patients had one or more enlarged EOM, of whom only 2 patients had clinical EOM dysfunction. Compared to Graves' disease patients with normal EOM volumes, those with EOM enlargement had significantly higher mean serum TSH (0.020 ± 0.005 versus 0.007 ± 0.002 mIU/L; P value 0.012), free-T4 (52.9 ± 3.3 versus 41.2 ± 1.7 pmol/L; P value 0.003) and technetium uptake on thyroid scintigraphy (13.51 ± 1.7% versus 8.55 ± 1.6%; P value 0.045). There were no differences between the 2 groups in anti-TSH-receptor antibody positivity, the proportion of males, tobacco smokers, or those with active ophthalmopathy. Conclusions. Patients with recently diagnosed Graves' disease and EOM volume enlargement have higher serum TSH and more severe hyperthyroidism than patients with normal EOM volumes, with no difference in anti-TSH-receptor antibody positivity between the two groups.

Pharmacological management of type 2 diabetes mellitus: an update.

While lifestyle modifications and metformin are the cornerstone of the initial management of type 2 diabetes mellitus, there is an increasing array of second and third-line pharmacological agents for this condition. These include sulphonylureas, insulin, thiazolidinediones and alpha-glucosidase inhibitors, with the more recent addition of glucagon- like peptide-1 agonists, dipeptidyl peptidase-IV inhibitors and pramlintide. Moreover, insulin analogues that better simulate endogenous insulin secretion have been developed. This review aims to provide an update on the current pharmacological management of type 2 diabetes mellitus, and to highlight the benefits and limitations of each treatment.