Executive summary of the SEORL CCC-SEEN consensus statement on post-thyroidectomy hypoparathyroidism. / Resumen ejecutivo del documento de consenso SEORL CCC-SEEN sobre hipoparatiroidismo postiroidectomía.

Hypoparathyroidism is the most common complication after total or completion thyroidectomy. It is defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels. Acute hypocalcemia is a potential lethal complication. Hypocalcemia treatment is based on endovenous or oral calcium supplements as well as oral calcitriol, depending on the severity of the symptoms. The risk of clinical hypocalcemia after bilateral thyroidectomy is considered very low if postoperative intact PTH decrease less than 80% with respect to preoperative levels. These patients could be discharged home without treatment, although this threshold may vary between institutions, and we recommend close surveillance in cases with increased risk (Graves disease, large goiters, reinterventions or evidence of parathyroid gland removal). Long-term treatment objectives are to control the symptoms and to keep serum calcium levels at the lower limit of the normal range, while preserving the calcium phosphate product and avoiding hypercalciuria.

Pycnogenol® prevents oxidative stress and side effects in patients with hypothyroidism during levothyroxine treatment.

BACKGROUND: In this study we aimed to evaluate the efficacy of Pycnogenol® supplementation in controlling oxidative stress levels and in reducing the frequency and severity of side effects of levothyroxine (LT4) treatment in patients who had recently started this therapy. METHODS: The registry included 60 females affected by primary hypothyroidism with multi-nodular goiter. LT4 was administered at the dosage of 100 µg/day.The registry study included only subjects under initial treatment, and followed up for a period of at least 30 days. A group took 150 mg Pycnogenol® daily and another served as control. RESULTS: The global occurrence of symptoms during the 30-day period was significantly lower with the supplement (P<0.05). CONCLUSIONS: Pycnogenol® may represent a useful tool to reduce LT4- related side effects in patients treated with hormone replacement therapy for hypothyroidism.

Long-Term Complications in Patients With Hypoparathyroidism Evaluated by Biochemical Findings: A Case-Control Study.

Hypoparathyroidism (HypoPT) is associated with an increased risk of various complications, but only few data are available on risk factors. Using a case-control design, we assessed associations between biochemical findings and risk of different complications within a subpopulation of our previously identified Danish patients. We retrieved all biochemical data available on 431 (81% women) patients from the Central Region of Denmark, covering approximately 20% of the Danish population. Average age of patients was 41 years at time of diagnosis. Most patients (88%) had HypoPT due to surgery, mainly due to atoxic goiter and more than 95% were on treatment with calcium supplements and activated vitamin D. On average, time-weighted (tw) plasma levels of ionized calcium (Ca2+tw ) was 1.17 mmol/L (interquartile range [IQR], 1.14 to 1.21 mmol/L) and the calcium-phosphate (CaxPtw ) product was 2.80 mmol2 /L2 (IQR, 2.51 to 3.03 mmol2 /L2 ). High phosphatetw levels were associated with increased mortality and risk of any infections, including infections in the upper airways. A high CaxPtw product was associated with an increased mortality and risk of renal disease. Compared to levels around the lower part of the reference interval, lower Ca2+tw levels were associated with an increased risk of cardiovascular diseases. Mortality and risk of infections, cardiovascular diseases, and renal diseases increased with number of episodes of hypercalcemia and with increased disease duration. Treatment with a relatively high dose of active vitamin D was associated with a decreased mortality and risk of renal diseases and infections. In conclusion, risk of complications in HypoPT is closely associated with disturbances in calcium-phosphate homeostasis. © 2018 American Society for Bone and Mineral Research.

Iodine Deficiency in a Parenteral Nutrition-Dependent Adolescent With Intestinal Pseudo-Obstruction.

Routine supplementation of iodine in parenteral nutrition (PN) solutions is not current practice in the United States. In this case study, we describe an incidental finding of goiter in a long-term PN-dependent adolescent. With increased iodine screening, we then identified additional patients with undetectable urinary iodine concentrations in our population of children with short bowel receiving long-term PN. We hypothesize that 2 practice changes are possibly reducing iodine provision to long-term PN-dependent patients: transition to alcohol-based skin preparations and lipid minimization.

[Effect of vitamin D deficiency on hypocalcaemia after total thyroidectomy due to benign goitre]. / Efecto de la deficiencia de vitamina D sobre la hipocalcemia tras tiroidectomía total por bocio benigno.

INTRODUCTION: The purpose of this study was to analyse the relationship between preoperative serum levels of vitamin D and postoperative hypocalcaemia after total thyroidectomy. MATERIAL AND METHODS: A prospective observational study was conducted on 113 patients treated by total thyroidectomy due to benign disease. Preoperative vitamin D serum levels and postoperative albumin-corrected calcium and parathormone (PTH) levels were determined. Sensitivity, specificity, positive predictive value and negative predictive value of vitamin D and PTH levels, respectively, in the diagnosis of postoperative hypocalcaemia were calculated. RESULTS: Hypocalcaemia was diagnosed in 44 (38.9%) patients. Vitamin D levels were significantly higher in the group of patients with normal postoperative calcium (median: 25.4pg/mL; range: 4-60), compared to those who developed hypocalcaemia (median: 16.4pg/mL; range: 6.3-46.9) (P=.001). Postoperative hypocalcaemia was more frequent in patients with vitamin D < 30ng/mL (39/78) (50%), than among those with normal levels (5/35) (14.2%) (P=.001). Sensitivity, specificity, positive predictive value and negative predictive value were 88% and 68%, 43% and 82%, 50% and 71%, and 85% and 80% for vitamin D and PTH, respectively. Vitamin D and PTH showed independent prognostic values on the risk of hypocalcaemia. The OR associated with vitamin D < 30ng/mL was 4.25 (95% CI: 1.31-13.78) (P=.016), and the OR of PTH<13pg/mL was 15.4 (95% CI: 4.83-49.1) (P<.001). CONCLUSION: Vitamin D deficiency is a risk factor of hypocalcaemia after total thyroidectomy for benign goitre. The vitamin D level provides independent prognostic information, which is complementary to that given by PTH.

Aspectos patogênicos e clínicos do bócio multinodular / Pathogenic and clinical aspects of multinodular goiter

O bócio multinodular (BMN) é definido como um aumento da glândula tireóide secundário à proliferação multifocal de tireócitos e caracteriza-se pela heterogeneidade no crescimento e função das células foliculares. O BMN é considerado uma neoplasia benigna da tireóide. É uma doença comum, com aumento da prevalência em áreas com deficiência de iodo, sendo este o principal fator etiológico ambiental. A patogênese desta disfunção tireoidiana ainda não está inteiramente elucidada. Nesta revisão serão abordados os principais mecanismos envolvidos na patogênese, seguidos das implicações clínicas dessa patologia.

Multinodular goiter (MNG) is defined as an enlargement of the thyroid gland that is characterized by heterogeneity in growth and function of thyroid follicular cells. MNG is now considered a true thyroid neoplasm. It is a common disease, with higher prevalences in iodine deficiency areas. Iodine deficiency is the main environmental etiologic factor for MNG. The pathogenesis of multinodular goiter is not yet fully clarified. The purpose of this review is to summarize the current knowledge of MNG with respect to the pathology, etiologic and clinical characteristics.

Localized attachment loss in Pendred syndrome: incidental?

BACKGROUND: Pendred syndrome is a rare, inherited, autosomal recessive disorder with an iodine organification defect of thyroxin produced by the thyroid gland. Its clinical features include sensorineural hearing loss, classically congenital and prelingual, and goiter. METHODS: This is the first case report of Pendred syndrome in the dental literature with oral findings that include localized extensive attachment loss involving mandibular incisor teeth and idiopathic hypercementosis involving multiple teeth in addition to other oral manifestations, suggesting hypothyroidism-like macroglossia and macrocheilia. Furthermore, serum alkaline phosphatase along with inorganic calcium and phosphate levels were also elevated. Peripheral neutrophil function test suggested a defective function of neutrophils. RESULTS: Management of the case included augmenting thyroxin supplementation, in consultation with an endocrinologist, and extraction of hopeless mandibular central incisors followed by placement of immediate transitional dentures. CONCLUSION: A comprehensive medical history and systemic and laboratory evaluations should be considered a prerequisite to identify, manage, and report such rare conditions in routine clinical practice.

Chronic iodine excess does not increase the incidence of hyperthyroidism: a prospective community-based epidemiological survey in China.

OBJECTIVE: An increasing incidence of hyperthyroidism has been observed when iodine supplementation has been introduced to an iodine-deficient population. Moreover, the influence of chronic more than adequate or excessive iodine intake on the epidemiological features of hyperthyroidism has not been widely and thoroughly described. To investigate the influences of different iodine intake levels on the incidence of hyperthyroidism, we conducted a prospective community-based survey in three communities with mild-deficient, more than adequate (previously mild deficient iodine intake), and excessive iodine intake. SUBJECTS AND METHODS: In three rural Chinese communities, a total of 3761 unselected inhabitants aged above 13 years participated in the original investigation and 3018 of them received identical examinations after 5 years. Thyroid function, levels of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody and urinary iodine excretion were measured and thyroid ultrasound examination was also performed. RESULTS: In three communities, median urinary iodine excretion was 88, 214, and 634 microg/l (P<0.05) respectively. The cumulative incidence of hyperthyroidism was 1.4, 0.9, and 0.8% (P>0.05) respectively. Autoimmune hyperthyroidism was predominant in thyroid hyperfunction in all the three cohorts. Either positive TPOAb (>50 U/ml) or goiter in original healthy participants was associated with the occurrence of unsuspected hyperthyroidism in 5 years (logistic regression, OR=4.2 (95% CI 1.7-8.8) for positive TPOAb, OR=3.1 (95% CI 1.4-6.8) for goiter). CONCLUSION: Iodine supplementation may not induce an increase in hyperthyroidism in a previously mildly iodine-deficient population. Chronic iodine excess does not apparently increase the risk of autoimmune hyperthyroidism, suggesting that excessive iodine intake may not be an environmental factor involved in the occurrence of autoimmune hyperthyroidism.

The importance of iodine nutrition during pregnancy.

OBJECTIVE: To examine the importance of iodine nutrition during pregnancy. DESIGN: Review of existing literature of iodine in pregnancy. SETTING: Population surveys and metabolic studies. SUBJECTS: Pregnant women. RESULTS: The main changes in thyroid function associated with pregnancy are due to an increase in hormone requirements that begin in the first trimester of gestation. This increase can only be met by a proportional increase in hormone production, something that depends directly upon the availability of iodine. When dietary iodine is lacking, an adequate physiological adaptation is difficult to achieve and is progressively replaced by pathological alterations that occur in parallel with the degree and duration of iodine deprivation. CONCLUSIONS: Iodine prophylaxis should be given systematically to women during pregnancy. In most public health programmes dealing with the correction of iodine deficiency disorders, iodised salt has been used as the preferred means to deliver iodine to households. Iodised salt, however, is not the ideal means of delivering iodine in the specific instances of pregnancy, breast-feeding and complementary feeding because of the need to limit salt intake during these periods. In European countries, presently it is proposed that iodine is given to pregnant women and breast-feeding mothers by systematically administering multivitamin tablets containing iodine in order to reach the recommended dietary allowance of 250 microg iodine day-1.

Iron deficiency in goitrous schoolchildren of Semirom, Iran.

BACKGROUND: Iodine deficiency produces the spectrum of iodine deficiency disorders (IDDs): endemic goiter, hypothyroidism, cretinism, and congenital anomalies. Other factors, including goitrogens and micronutrient deficiencies, may influence the prevalence and severity of IDDs and response to iodine supplementation. This cross-sectional, descriptive study was performed in 2003 on elementary school children of Semirom, a mountainous region of Iran, where goiter was hyper-endemic in 1994, but the goiter prevalence had not decreased as expected many years after salt iodization and iodine injection. Some possible risk factors associated with goiter in that area were evaluated, and the results of iron study are presented here. METHODS: 1,869 cases were selected by a multistage cluster sampling procedure. Grade 2 goitrous children were compared with equal number of nongoitrous children for serum iron, ferritin, transferrin, thyroxin, TSH and urine iodine concentrations (UIC). RESULTS: 210 children (105 goiter grade 0 and 105 goiter grade 2) entered this sub-study. Of 210 participants, 70 children had low transferrin saturation, 13 had low serum ferritin and 9 children had both problems. There was no significant difference in goiter rate between children with low iron indices and others. There was no significant correlation between serum iron, ferritin or transferrin saturation with other variables including T4, UIC and goiter stage. CONCLUSION: The present study reveals that in the area studied, iron deficiency cannot explain the high prevalence of goiter, so other responsible factors should be investigated.

Hypothyroid goitre in a ram: chemical analysis gives indirect evidence for a structurally altered type of ovine thyroglobulin.

The thyroglobulin of a ram of the East Friesian milk sheep breed suffering from goitre was investigated by physico- and immunochemical methods. The respective ram was the only animal amongst the other sheep of the flock, that exhibited severe goitre, additionally showing depressed behaviour. Results of the thyroid-stimulating hormone response test were indicative of hypothyroidism. The dysfunction of the thyroid gland could be treated by additional iodine supplementation quite successfully, although all sheep had been given iodinated cattle salt throughout the course of the history. Without reducing conditions sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of isolated thyroglobulin molecules of the ram and control sheep did not reveal different band patterns, but under reducing conditions different band patterns were evident for the respective animals: the ram's thyroglobulin displayed two main bands, those of healthy reference sheep only one. Both bands reacted equally with anti-thyroglobulin antibodies, even with those produced by immunizing rabbits with single bands. The reduced single thyroglobulin band of healthy sheep corresponded to a truncated form of that molecule, whereas the additional main band of the ram was a more resistant, intact thyroglobulin subunit, as was shown by mass spectrometry. In conclusion, results of physico- and immunochemical investigations gave evidence of a modification of thyroglobulin with suspected different iodine binding properties in the ram. The latter finding may have clinical relevance in similar cases in other species, as it is an example of the impact that a minor change in a protein molecule may have on a complete metabolic pathway. Additionally, it could be shown, that in the ovine species the generally found single main band of thyroglobulin after reduction is a truncated form and not an intact subunit. This truncation seems to be induced in vitro by the reductive sample pretreatment prior to SDS-PAGE.

Dual fortification of salt with iodine and microencapsulated iron: a randomized, double-blind, controlled trial in Moroccan schoolchildren.

BACKGROUND: In many developing countries, children are at high risk of both goiter and iron deficiency anemia. OBJECTIVE: In a series of studies in northern Morocco, we developed and tested a dual-fortified salt (DFS) containing iodine and microencapsulated iron. DESIGN: To establish the DFS fortification concentration, we measured salt intake by 3-d weighed food records and estimated iron bioavailability from the local diet by using published algorithms. We then formulated a DFS containing 25 micro g iodine/g salt (as potassium iodide) and 1 mg iron/g salt (as ferrous sulfate hydrate encapsulated with partially hydrogenated vegetable oil). After storage and acceptability trials, we compared the efficacy of the DFS to that of iodized salt in a 9-mo, randomized, double-blind trial in iodine-deficient, 6-15-y-old children (n = 377). RESULTS: Mean salt intake in school-age children was 7-12 g/d, and estimated iron bioavailability from the local diet was 0.4-4.3%. After storage for 20 wk, the DFS and iodized salt were not significantly different in iodine content, and color stability was acceptable when the compounds were added to local meals. During the efficacy trial, urinary iodine concentrations and thyroid volumes improved significantly (P < 0.001 and < 0.05, respectively) from baseline in both groups. At 40 wk, mean hemoglobin concentrations in the DFS group had increased by 14 g/L (P < 0.01), and serum ferritin, transferrin receptor, and zinc protoporphyrin concentrations were significantly better (P < 0.05) in the DFS group than in the iodized salt group. The prevalence of iron deficiency anemia in the DFS group decreased from 35% at baseline to 8% at 40 wk (P < 0.001). CONCLUSION: A DFS containing iodine and encapsulated iron can be an effective fortification strategy.

Physiology and pharmacology of iodized oil in goiter prophylaxis.

Thyroid complications resulting from excess iodide such as thyrotoxicosis, thyroiditis, sialadenitis, or hypothyroidism are much rarer after iodine supplementation with Lipiodol than with KI. They do not militate against its widespread use in endemic goiter populations, especially in pregnant women. However, patients with multinodular goiter should not be treated or should be treated only under careful observation. When Lipiodol-induced thyrotoxicosis occurs it tends to be mild or even subclinical and self-limited. If treatment is required, potassium perchlorate with or without thionamides is recommended. Iodide goiter has not been seen after Lipiodol supplementation, nor has thyroiditis. Sialadenitis occurs rarely. Iodide derived from Lipiodol readily enters the fetus, possibly by active transport, and theoretically endangers the fetus because autoregulation of the fetal thyroid occurs late during gestation. Despite the difficulty in distinguishing iodide goiter from iodide deficiency goiter of the newborn, no cases of neonatal iodide goiter have been reported. Possible mechanisms of thyroid inhibition by excess iodide are briefly discussed. The use of locally produced iodized plant oils is recommended for financial reasons as well as for the benefits derived from local participation.

Oftalmopatía de Graves y disfunción tiroidea: hipertiroidismo e hipotiroidismo / Grave's ophtalmopathy and thyroid dysfunction: hyperthyroidism and hypothyroidism

Se presenta el caso de dos pacientes adoles-centes con oftalmopatía infltrativa y bocio difuso, pero con una afectación funcional tiroidea muy distinta: hipertiroidismo (enfermedad de Graves) e hipotiroidismo (tiroiditis de Hashimoto). A la oftalmopatía tiroidea o de Graves cabría considerarla como una entidad nosológica propia que, si bien generalmente se acompañará de tirotoxicosis, puede asociarse con alteraciones tiroideas muy variadas (AU)

Postural changes of the cervical spine in patients with nontoxic goiter.

PURPOSE: To investigate differences in cervical spine posture and range of motion and self-reported neck pain and headache between patients with nontoxic goiter compared with a matched control group. DESIGN: An observational, controlled, blinded study. SETTING: The ambulatory outpatient facility of a university hospital. PARTICIPANTS: Twenty-five nontoxic goiter patients and 25 matched nongoiterous control subjects from the Department of Endocrinology. INTERVENTION: Participants were X-rayed from a lateral position in neutral, full flexion and full extension, and the radiographs were evaluated by a blinded examiner for anterior head carriage, maximal flexion, maximal extension and the extent and severity of any degenerative changes in the cervical spine. The degree of postural neck muscle tenderness was evaluated by a blinded rheumatologist using a validated Total Tenderness Score system. In addition, the two groups were compared for their self-reported frequency of neck pain and headaches. RESULTS: A significant increase in anterior head carriage was found among the goiter patients (p = .01), together with a corresponding decrease in flexion (p = .01), whereas the corresponding increase in extension was not statistically significant (p = .16). A higher prevalence of headaches was found in the goiter group (p = .06), but there was no difference in neck muscle tenderness (p = .40) or frequency of neck problems (p = .40) between the groups. The severity of degenerative changes in the cervical spine (p = .22) and the number of vertebral levels with degenerative changes (p = .13) were similar in the two groups. CONCLUSIONS: Goiters of > 100 g seem to alter the posture of the cervical spine, possibly resulting in a tendency for more frequent headaches. The changes do not seem to cause more neck pain, muscle tenderness or degeneration of the cervical spine.

Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status.

BACKGROUND AND METHODS: Kashin-Beck disease is a degenerative osteoarticular disorder that is endemic to certain areas of Tibet, where selenium deficiency is also endemic. Because selenium is involved in thyroid hormone metabolism, we studied the relation among the serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects 5 to 15 years of age in 12 villages around Lhasa, Tibet, including 1 control village in which no subject had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. RESULTS: Among the 575 subjects, 280 (49 percent) had Kashin-Beck disease, 267 (46 percent) had goiter, and 7 (1 percent) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66 percent had a urinary iodine concentration of less than 2 microg per deciliter (157 nmol per liter; normal, 5 to 25 microg per deciliter [394 to 1968 nmol per liter]). The mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects (1.2 vs. 1.8 microg per deciliter [94 vs. 142 nmol per liter], P<0.001) and hypothyroidism was more frequent (23 percent vs. 4 percent, P=0.01). Severe selenium deficiency was documented in all villages; 38 percent of subjects had serum concentrations of less than 5 ng per milliliter (64 nmol per liter; normal, 60 to 105 ng per milliliter [762 to 1334 nmol per liter]). When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not. CONCLUSIONS: In areas where severe selenium deficiency is endemic, iodine deficiency is a risk factor for Kashin-Beck disease.

PIP: Selenium is involved in thyroid hormone metabolism. Kashin-Beck disease is a degenerative osteoarticular disorder endemic to certain areas of Tibet, where selenium deficiency is also endemic. Findings are reported from an investigation of the relationship among serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects aged 5-15 years in 12 villages around Lhasa, Tibet, including 1 control village in which no one had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. 280 (49%) subjects had Kashin-Beck disease, 267 (46%) had goiter, and 7 (1%) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66% had a urinary iodine concentration of less than 2 mcg/dl. Mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects and hypothyroidism was more frequent. Severe selenium deficiency was documented in all villages, with 38% of subjects having serum concentrations of less than 5 ng/ml. When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not.

Thyrotoxicosis in Zaria, Nigeria: an update.

The total number of operations performed for thyroid diseases at the ABU Teaching Hospital, Zaria from January 1986 to December 1995 has reduced. Those performed for thyrotoxicosis have tripled (18.5% of all thyroid operations compared to 5.7% ten years ago). Younger patients (mean age 27.7 years, range 13-15 years) with thyrotoxicosis are being seen but the clinical features of the disease and its management at the centre have not changed. It is suggested that the apparent increase in incidence and earlier onset of thyrotoxicosis in this environment may be due to the increasing use of iodised salt to combat endemic goitre.

Differentiated thyroid cancer: surgical treatments of 190 patients.

Between 1968 and 1991, 190 patients (51 men, 139 women) with a mean age of 46.3 years underwent surgery for differentiated thyroid cancer (148 papillary and 42 follicular carcinomas). In 29.5% of the cases a concomitant goitre was histologically demonstrated. These patients were significantly older (mean: 54.7 years) (P<0.01). The patients who had previously received cervical radiotherapy were significantly younger (mean: 29.7 years) (P<0.01). The analysis of historical and clinical findings failed to identify predictive factors of biological aggressiveness. Hyperthyroidism occurred in 5.7% of patients: this subgroup did not show any difference in clinical behaviour. Occult carcinoma (14.7%) and multifocality (9.4%) were found more frequently in the glands with a pre-existent goitre (P<0.05), but the clinical significance of these aspects is uncertain. The surgical treatment of choice was total thyroidectomy (135 patients); more conservative procedures were performed only in younger patients with small lesions, without a difference in survival. Post-operatively a permanent recurrent laryngeal nerve injury occurred in four patients (2.1%) and nine patients (4.7%) required a permanent calcium supplementation. Among patients in follow-up (91.6%), those who underwent a total thyroidectomy were studied using a total body scinti scan. A poor prognosis was associated with age (>40 years), pT, stage, pM and symptomatic metastases.