A hospital based epidemiological study of genetically determined muscle disease in south western Norway

We determined the prevalence of genetically determined neuromuscular diseases in adult Norwegian patients from Hordaland County. We identified patients using International Classification of Disease codes registered in our hospital database and reviewed patient notes to ensure diagnostic accuracy. To ensure maximal ascertainment, we screened both inpatient and outpatient contacts from two 5-year periods 01.01.2005 to 31.12.2009 and 01.01.2008 to 01.01.2013, and used the second data set to define prevalence. Myotonic dystrophy was the commonest adult muscle disorder with a minimum prevalence of 11.84/100,000 followed by facioscapulohumeral muscular dystrophy at 6.42/100,000. Genetically confirmed limb-girdle muscular dystrophies had a prevalence of 4.2/100,000 with CAPN3 mutations being the commonest followed by mutations in ANO5 and FKRP. Becker muscular dystrophy was rare (0.4/100,000). For the purposes of comparison, we also ascertained adults with spinal muscular atrophy (SMA) and found a prevalence of 4.42/100,000. The impact of neuromuscular disease is enormous both for the patient and for society. Progressive weakness and increasing dependency together with pulmonary and cardiac complications require specialised, multidisciplinary follow up. The provision of such care places substantial demands on health service resources. Thus, precise understanding of both type of neuromuscular disease and numbers of patients is essential in order to manage individuals appropriately and plan future health service needs.publishedVersio

Infant iodine status and associations with maternal iodine nutrition, breastfeeding status and thyroid function

Adequate iodine nutrition during infancy is required for normal thyroid function and, subsequently, brain development. However, data on infant iodine status in the first year of life are scarce. This study aimed to describe infant iodine status and further explore its associations with maternal iodine nutrition, breast-feeding status and thyroid function. In this cohort study, 113 infants were followed up at ages 3, 6 and 11 months in Norway. Infant and maternal urinary iodine concentration (UIC), maternal iodine intake, breast milk iodine concentration (BMIC), breast-feeding status and infant thyroid function tests were measured. The median infant UIC was 82 µg/l at the age of 3 months and below the WHO cut-off of 100 µg/l. Infant UIC was adequate later in infancy (median 110 µg/l at ages 6 and 11 months). Infant UIC was associated positively with maternal UIC (β = 0·33, 95 % CI (0·12, 0·54)), maternal iodine intake (β = 0·30, 95 % CI (0·18, 0·42)) and BMIC (β = 0·46, 95 % CI (0·13, 0·79)). Breastfed infants had lower median UIC compared with formula-fed infants at ages 3 months (76 v. 190 µg/l) and 6 months (105 v. 315 µg/l). Neither infant UIC nor BMIC were associated with infant thyroid function tests. In conclusion, breastfed infants in Norway are at risk of insufficient iodine intake during the first months of life. Maternal iodine nutrition is important for providing sufficient iodine intake in infants, and awareness of promoting adequate iodine nutrition for lactating women should be prioritised.publishedVersio

Iodine Nutrition and Iodine Supplement Initiation in Association with Thyroid Function in Mildly-to-Moderately Iodine-Deficient Pregnant and Postpartum Women

Background Whereas the adverse effects of severe iodine deficiency during pregnancy are well documented, the effects of mild-to-moderate deficiency are not well established. Objectives We aimed to explore whether iodine nutrition and timing of iodine supplement initiation are associated with thyroid function in pregnant and postpartum women. Methods In this cohort study, 137 pregnant women were enrolled and followed up at gestational weeks (GWs) 18 and 36, and 3 and 6 mo postpartum. Thyroid function tests [thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)], urinary iodine and creatinine concentration (UIC:Cr), and iodine intake (including iodine supplement use) were measured at each time point. The associations between thyroid hormone concentrations and UIC:Cr, iodine intakes, and iodine supplement use were estimated using multiple generalized estimating equation models. Results The median UIC at GW18 was 94 μg/L, indicating mild-to-moderate iodine deficiency. UIC:Cr (β; 95% CI) per 100 μg/g was negatively associated with fT3 (−0.191; −0.331, −0.051) and fT4 (−0.756; −1.372, −0.141) concentrations. Iodine intake (β; 95% CI) per 100 μg/d was positively associated with TSH (0.099; 0.022, 0.177), and negatively associated with fT3 (−0.084; −0.0141, −0.027) and fT4 (−0.390; −0.599, −0.182) concentrations. Compared with no use of supplement, those initiating an iodine-containing supplement prepregnancy and continuing through pregnancy had lower TSH (estimated means) (1.35 compared with 1.68 mIU/L, P = 0.021), and higher fT3 (4.48 compared with 4.28 pmol/L, P = 0.035) and fT4 (15.2 compared with 14.4 pmol/L, P = 0.024) concentrations. Conclusions Lower iodine availability during pregnancy and postpartum was associated with lower TSH, and higher fT3 and fT4 concentrations. The use of an iodine-containing supplement that was initiated prepregnancy and continuing through pregnancy was associated with lower TSH, and higher fT3 and fT4 concentrations, which may suggest improved thyroid function. These findings support the notion that optimization of iodine intake should start before pregnancy. This trial was registered at clinicaltrials.gov as NCT02610959.publishedVersio

Substantial changes in inflammatory and cardiovascular biomarkers in patients with autonomous cortisol secretion

Objective To map inflammatory biomarkers in patients with autonomous cortisol secretion (ACS) and overt Cushing syndrome (CS). Method Observational study including serum from prospectively included patients with ACS (n = 63), adrenal CS (n = 2), pituitary CS (n = 8), and healthy subjects (n = 120). Serum samples were analysed for 92 inflammatory biomarkers using proximity extension assay (OLINK). Results Combined, the ACS and CS patients displayed significant differences in levels of 49/92 inflammatory biomarkers (46 increased/3 decreased) compared with healthy controls. No differences in biomarker levels were found between ACS and overt CS, and none of the biomarkers correlated with the degree of hypercortisolism. Postoperative samples were available for 17 patients, median 24 months (range 6–40) after surgery and biochemical curation. There was no significant normalization of the biomarkers postoperatively. Conclusion There was a systemic rise in inflammatory biomarkers in patients with ACS and CS, not correlated to the degree of hypercortisolism. These biomarkers were not normalized following biochemical cure.publishedVersio

Systemic Activation of the Kynurenine Pathway in Graves Disease With and Without Ophthalmopathy

Context Graves disease (GD) is one of the most common autoimmune disorders. Recent literature has shown an immune response involving several different inflammatory related proteins in these patients. Objective This work aimed to characterize the kynurenine pathway, activated during interferon-γ (IFN-γ)–mediated inflammation and cellular (T-helper type 1 [Th1] type) immunity, in GD patients with and without thyroid eye disease (TED). Methods We analyzed 34 biomarkers by mass spectrometry in serum samples from 100 patients with GD (36 with TED) and 100 matched healthy controls. The analytes included 10 metabolites and 3 indices from the kynurenine pathway, 6 microbiota-derived metabolites, 10 B-vitamers, and 5 serum proteins reflecting inflammation and kidney function. Results GD patients showed significantly elevated levels of 7 biomarkers compared with healthy controls (omega squared [ω2] > 0.06; P < .01). Of these 7, the 6 biomarkers with the strongest effect size were all components of the kynurenine pathway. Factor analysis showed that biomarkers related to cellular immunity and the Th1 responses (3-hydroxykynurenine, kynurenine, and quinolinic acid with the highest loading) were most strongly associated with GD. Further, a factor mainly reflecting acute phase response (C-reactive protein and serum amyloid A) showed weaker association with GD by factor analysis. There were no differences in biomarker levels between GD patients with and without TED. Conclusion This study supports activation of IFN-γ inflammation and Th1 cellular immunity in GD, but also a contribution of acute-phase reactants. Our finding of no difference in systemic activation of the kynurenine pathway in GD patients with and without TED implies that the local Th1 immune response in the orbit is not reflected systemically.publishedVersio

Myxedema coma complicated by bilateral hygromas

Myxedema coma is an important differential diagnosis in critically ill patients. Early diagnosis and treatment are paramount but challenging due to a lack of diagnostic criteria. We report a case about a patient who suffered from untreated hypothyroidism for several years. Before the correct diagnosis was made, he was admitted three times due to severe constipation. Eventually, he developed myxedema coma in connection with a urinary tract infection. The course was complicated by recurrent seizures, and neuroimaging showed bilateral hygromas. Hormone replacement therapy resulted in complete recovery and regression of hygromas. To the best of our knowledge, this is the first time hygroma is reported in association with myxedema coma

Iodine Nutrition and Iodine Supplement Initiation in Association with Thyroid Function in Mildly-to-Moderately Iodine-Deficient Pregnant and Postpartum Women

Background Whereas the adverse effects of severe iodine deficiency during pregnancy are well documented, the effects of mild-to-moderate deficiency are not well established. Objectives We aimed to explore whether iodine nutrition and timing of iodine supplement initiation are associated with thyroid function in pregnant and postpartum women. Methods In this cohort study, 137 pregnant women were enrolled and followed up at gestational weeks (GWs) 18 and 36, and 3 and 6 mo postpartum. Thyroid function tests [thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)], urinary iodine and creatinine concentration (UIC:Cr), and iodine intake (including iodine supplement use) were measured at each time point. The associations between thyroid hormone concentrations and UIC:Cr, iodine intakes, and iodine supplement use were estimated using multiple generalized estimating equation models. Results The median UIC at GW18 was 94 μg/L, indicating mild-to-moderate iodine deficiency. UIC:Cr (β; 95% CI) per 100 μg/g was negatively associated with fT3 (−0.191; −0.331, −0.051) and fT4 (−0.756; −1.372, −0.141) concentrations. Iodine intake (β; 95% CI) per 100 μg/d was positively associated with TSH (0.099; 0.022, 0.177), and negatively associated with fT3 (−0.084; −0.0141, −0.027) and fT4 (−0.390; −0.599, −0.182) concentrations. Compared with no use of supplement, those initiating an iodine-containing supplement prepregnancy and continuing through pregnancy had lower TSH (estimated means) (1.35 compared with 1.68 mIU/L, P = 0.021), and higher fT3 (4.48 compared with 4.28 pmol/L, P = 0.035) and fT4 (15.2 compared with 14.4 pmol/L, P = 0.024) concentrations. Conclusions Lower iodine availability during pregnancy and postpartum was associated with lower TSH, and higher fT3 and fT4 concentrations. The use of an iodine-containing supplement that was initiated prepregnancy and continuing through pregnancy was associated with lower TSH, and higher fT3 and fT4 concentrations, which may suggest improved thyroid function. These findings support the notion that optimization of iodine intake should start before pregnancy. This trial was registered at clinicaltrials.gov as NCT02610959

Infant iodine status and associations with maternal iodine nutrition, breastfeeding status and thyroid function

Adequate iodine nutrition during infancy is required for normal thyroid function and, subsequently, brain development. However, data on infant iodine status in the first year of life are scarce. This study aimed to describe infant iodine status and further explore its associations with maternal iodine nutrition, breast-feeding status and thyroid function. In this cohort study, 113 infants were followed up at ages 3, 6 and 11 months in Norway. Infant and maternal urinary iodine concentration (UIC), maternal iodine intake, breast milk iodine concentration (BMIC), breast-feeding status and infant thyroid function tests were measured. The median infant UIC was 82 µg/l at the age of 3 months and below the WHO cut-off of 100 µg/l. Infant UIC was adequate later in infancy (median 110 µg/l at ages 6 and 11 months). Infant UIC was associated positively with maternal UIC (β = 0·33, 95 % CI (0·12, 0·54)), maternal iodine intake (β = 0·30, 95 % CI (0·18, 0·42)) and BMIC (β = 0·46, 95 % CI (0·13, 0·79)). Breastfed infants had lower median UIC compared with formula-fed infants at ages 3 months (76 v. 190 µg/l) and 6 months (105 v. 315 µg/l). Neither infant UIC nor BMIC were associated with infant thyroid function tests. In conclusion, breastfed infants in Norway are at risk of insufficient iodine intake during the first months of life. Maternal iodine nutrition is important for providing sufficient iodine intake in infants, and awareness of promoting adequate iodine nutrition for lactating women should be prioritised

Infant iodine status and associations with maternal iodine nutrition, breastfeeding status and thyroid function

Adequate iodine nutrition during infancy is required for normal thyroid function and, subsequently, brain development. However, data on infant iodine status in the first year of life are scarce. This study aimed to describe infant iodine status and further explore its associations with maternal iodine nutrition, breast-feeding status and thyroid function. In this cohort study, 113 infants were followed up at ages 3, 6 and 11 months in Norway. Infant and maternal urinary iodine concentration (UIC), maternal iodine intake, breast milk iodine concentration (BMIC), breast-feeding status and infant thyroid function tests were measured. The median infant UIC was 82 µg/l at the age of 3 months and below the WHO cut-off of 100 µg/l. Infant UIC was adequate later in infancy (median 110 µg/l at ages 6 and 11 months). Infant UIC was associated positively with maternal UIC (β = 0·33, 95 % CI (0·12, 0·54)), maternal iodine intake (β = 0·30, 95 % CI (0·18, 0·42)) and BMIC (β = 0·46, 95 % CI (0·13, 0·79)). Breastfed infants had lower median UIC compared with formula-fed infants at ages 3 months (76 v. 190 µg/l) and 6 months (105 v. 315 µg/l). Neither infant UIC nor BMIC were associated with infant thyroid function tests. In conclusion, breastfed infants in Norway are at risk of insufficient iodine intake during the first months of life. Maternal iodine nutrition is important for providing sufficient iodine intake in infants, and awareness of promoting adequate iodine nutrition for lactating women should be prioritised

Iodine nutrition and iodine supplement initiation in association with thyroid function in mildly-to-moderately iodine-deficient pregnant and postpartum women

Background: Whereas the adverse effects of severe iodine deficiency during pregnancy are well documented, the effects of mild-to-moderate deficiency are not well established. Objectives: We aimed to explore whether iodine nutrition and timing of iodine supplement initiation are associated with thyroid function in pregnant and postpartum women. Methods: In this cohort study, 137 pregnant women were enrolled and followed up at gestational weeks (GWs) 18 and 36, and 3 and 6 mo postpartum. Thyroid function tests [thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4)], urinary iodine and creatinine concentration (UIC:Cr), and iodine intake (including iodine supplement use) were measured at each time point. The associations between thyroid hormone concentrations and UIC:Cr, iodine intakes, and iodine supplement use were estimated using multiple generalized estimating equation models. Results: The median UIC at GW18 was 94 μg/L, indicating mild-to-moderate iodine deficiency. UIC:Cr (β; 95% CI) per 100 μg/g was negatively associated with fT3 (-0.191; -0.331, -0.051) and fT4 (-0.756; -1.372, -0.141) concentrations. Iodine intake (β; 95% CI) per 100 μg/d was positively associated with TSH (0.099; 0.022, 0.177), and negatively associated with fT3 (-0.084; -0.0141, -0.027) and fT4 (-0.390; -0.599, -0.182) concentrations. Compared with no use of supplement, those initiating an iodine-containing supplement prepregnancy and continuing through pregnancy had lower TSH (estimated means) (1.35 compared with 1.68 mIU/L, P = 0.021), and higher fT3 (4.48 compared with 4.28 pmol/L, P = 0.035) and fT4 (15.2 compared with 14.4 pmol/L, P = 0.024) concentrations. Conclusions: Lower iodine availability during pregnancy and postpartum was associated with lower TSH, and higher fT3 and fT4 concentrations. The use of an iodine-containing supplement that was initiated prepregnancy and continuing through pregnancy was associated with lower TSH, and higher fT3 and fT4 concentrations, which may suggest improved thyroid function. These findings support the notion that optimization of iodine intake should start before pregnancy.This trial was registered at clinicaltrials.gov as NCT02610959. Keywords: iodine; iodine deficiency; iodine supplementation; pregnancy; thyroid hormones. © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition