Low Thyroxine Research Articles

Thyroid screening in pregnancy

The adverse impact of overt hypothyroidism that complicates pregnancy outcomes is well-established and not debated. For more than a decade, however, endocrinologists and obstetricians have been debating whether screening for subclinical thyroid disorders during pregnancy should be routine or should continue to be based on symptoms and risk factors. Several observational studies have suggested that offspring of women with asymptomatic thyroid dysfunction were at increased risk for impaired neurodevelopment. Other studies have suggested that pregnant women with subclinical thyroid disease, particularly those identified with an elevated thyroid-stimulating hormone (TSH) level may be at increased risk for pregnancy complications such as fetal death, preterm birth, or placental abruption. These data have prompted both obstetric and endocrinologic professional societies to draft recommendations regarding screening for thyroid disease during pregnancy, some of which are not entirely based on available evidence. The prevalence of overt thyroid disease is estimated to be 1-2 per 1000 pregnancies and historically has not been considered high enough to justify routine screening. Lower TSH thresholds (>2.5 mU/L) for the diagnosis of hypothyroidism have been promoted, and women with subclinical thyroid dysfunction commonly are included in estimates of thyroid disease during pregnancy, both of which exaggerate prevalence rates. The most compelling recent evidence on this issue has come from the Controlled Antenatal Thyroid Screening trial. After almost 22,000 pregnant women were screened for either isolated high TSH or isolated low free thyroxine level, 390 children of treated women with either diagnosis were compared with 404 children of similar women who were not treated during pregnancy. Treatment had no effect on mean offspring IQ at age 3 years or the number of children with an IQ <85. Authors of this landmark study concluded that antenatal screening and maternal treatment for women with subclinical thyroid dysfunction did not result in improved cognitive function. An ongoing intervention trial conducted by the Eunice Kennedy-Shriver National Institute of Child Health and Human Development's Maternal-Fetal Medicine Units Network will provide further clarity to this important question. In the interim, the debating authors have concluded, after careful review of the currently published literature, that routine screening for subclinical thyroid dysfunction during pregnancy is not currently warranted at this time.

Non-thyroidal illness in the ICU: a syndrome with different faces.

Critically ill patients typically present with low or low-normal plasma thyroxine, low plasma triiodothyronine (T3), increased plasma reverse T3 (rT3) concentrations, in the absence of a rise in thyrotropin (TSH). This constellation is referred to as nonthyroidal illness syndrome (NTI). Although it is long known that the severity of NTI is associated with risk of poor outcomes of critical illness, the causality in this association has not been well investigated. In this narrative review, the different faces of NTI during critical illness are highlighted. Acute alterations are dominated by changes in thyroid hormone binding, peripheral thyroid hormone uptake, and alterations in the expression and activity of the type-1 and type-3 deiodinases. It was recently shown that at least part of these acute changes are brought about by concomitant macronutrient restriction, and this part appears adaptive and beneficial. However, the face of the NTI in the prolonged phase of critical illness is different, when patients are fully fed but continue to depend on intensive medical care. In that prolonged phase of illness, hypothalamic thyrotropin releasing hormone (TRH) expression is suppressed and explains reduced TSH secretion and whereby reduced thyroidal hormone release. During prolonged critical illness, and in the presence of adequate nutrition, several tissue responses could be interpreted as compensatory to low thyroid hormone availability, such as increased expression of monocarboxylate transporters, upregulation of type-2 deiodinase activity, and increased sensitivity at the receptor level. Infusing hypothalamic releasing factors in these prolonged critically ill patients can reactivate the thyroid axis and induce an anabolic response. It is clear that the name "NTI" during critical illness refers to a syndrome with different faces. Tolerating the early "fasting response" to critical illness and its concomitant changes in thyroid hormone parameters appears to be wise and beneficial. This thus applies to the NTI present in the majority of the patients treated in intensive care units. However, the NTI that occurs in prolonged critically ill patients appears different with regard to both its causes and consequences. Future studies should specifically target this selected population of prolonged critically ill patients, and, after excluding iatrogic drug interferences, investigate the effect on outcome of treatment with hypothalamic releasing factors in adequately powered randomized controlled trials.

Lipid Profile of Patients with Thyroid Dysfunction in Ayurveda Hospital

Background : Thyroid hormones play an indispensable role in various metabolic processes in the human body. Thyroid disorders other than iodine deficiency disorders in the form of thyroiditis, hypothyroidism or autoimmune thyroid dysfunctions are on rise. Objective : This study was done to study the prevalence and pattern of dyslipidemia in patients with thyroid dysfunction. Methods : It is a retrospective study based on the available biochemical data of 50 thyroid patients (33 females and 17 males) with age range of 26-68 years. Serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) triiodothyronine (T 3 ), thyroxine (T 4 ) and thyroid stimulating hormone (TSH), were measured using standard assays procedures. Results: The results showed that 82% of the study population has hypothyroidism with the higher prevalence among females. The mean values of T 3 , T 4 and TSH in patients with thyroid dysfunction were 0.8 0.05 ng/ml, 4.2 0.5 mg/dl and 9.45 1.2 mIU/ml, respectively. The mean values of TC, TG, HDL-C, LDL-C, and VLDL-C were 222.4 3.8 mg/dl, 180.3 8.2 mg/dl, 35.6 1.3 mg/dl, 151.6 6.2 mg/dl and 36.5 2.6 mg/dl respectively in patients with hypothyroidism. Hypothyroidism shows significant positive correlation with TC, TG and LDL. Results show that even a slight increase in serum TSH showed significant dyslipidemia. Conclusion : This study suggests that regular monitoring of lipid level in patients with thyroid dysfunction would be helpful in preventing cardiovascular diseases.

Leptin ameliorates insulin resistance and hepatic steatosis in Agpat2−/− lipodystrophic mice independent of hepatocyte leptin receptors

Leptin is essential for energy homeostasis and regulation of food intake. Patients with congenital generalized lipodystrophy (CGL) due to mutations in 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) and the CGL murine model (Agpat2(-/-) mice) both have severe insulin resistance, diabetes mellitus, hepatic steatosis, and low plasma leptin levels. In this study, we show that continuous leptin treatment of Agpat2(-/-) mice for 28 days reduced plasma insulin and glucose levels and normalized hepatic steatosis and hypertriglyceridemia. Leptin also partially, but significantly, reversed the low plasma thyroxine and high corticosterone levels found in Agpat2(-/-) mice. Levels of carbohydrate response element binding protein (ChREBP) were reduced, whereas lipogenic gene expression were increased in the livers of Agpat2(-/-) mice, suggesting that deregulated ChREBP contributed to the development of fatty livers in these mice and that this transcription factor is a target of leptin's beneficial metabolic action. Leptin administration did not change hepatic fatty acid oxidation enzymes mRNA levels in Agpat2(-/-) mice. The selective deletion of leptin receptors only in hepatocytes did not prevent the positive metabolic actions of leptin in Agpat2(-/-) mice, supporting the notion that the majority of metabolic actions of leptin are dependent on its action in nonhepatocyte cells and/or the central nervous system.

Muscle Disease

On the basis of strong research evidence, Duchenne muscular dystrophy (DMD), the most common severe childhood form of muscular dystrophy, is an X-linked recessive disorder caused by out-of-frame mutations of the dystrophin gene. Thus, it is classified asa dystrophinopathy. The disease onset is before age 5 years. Patients with DMD present with progressive symmetrical limb-girdle muscle weakness and become wheelchair dependent after age 12 years. (2)(3). On the basis of some research evidence,cardiomyopathy and congestive heart failure are usually seen in the late teens in patients with DMD. Progressive scoliosis and respiratory in sufficiency often develop once wheelchair dependency occurs. Respiratory failure and cardiomyopathy are common causes of death, and few survive beyond the third decade of life. (2)(3)(4)(5)(6)(7). On the basis of some research evidence, prednisone at 0.75 mg/kg daily (maximum dose, 40 mg/d) or deflazacort at 0.9 mg/kg daily (maximum dose, 39 mg/d), a derivative of prednisolone (not available in the United States), as a single morning dose is recommended for DMD patients older than 5 years, which may prolong independent walking from a few months to 2 years. (2)(3)(16)(17). Based on some research evidence, treatment with angiotensin-converting enzyme inhibitors, b-blockers, and diuretics has been reported to be beneficial in DMD patients with cardiac abnormalities. (2)(3)(5)(18). Based on expert opinion, children with muscle weakness and increased serum creatine kinase levels may be associated with either genetic or acquired muscle disorders (Tables 1 and 3). (14)(15)

Central hypothyroidism in children.

Central congenital hypothyroidism (CCH) is an underdiagnosed disorder poorly described in childhood and adolescence. Congenital defects in thyroid-stimulating hormone (TSH) synthesis, secretion or bioactivity may lead to a state of 'regulatory' hypothyroidism expressed through aberrantly low or normal TSH levels and low thyroxine (T4), a hormonal pattern undetectable by TSH-based neonatal screening programs for congenital hypothyroidism (CH) implemented in most countries worldwide. CCH is more prevalent than previously thought, reaching 1 in 16,000 neonates in countries consistently identifying CCH through T4-based CH screening strategies. Neonatal detection and early treatment of CCH would prevent the risk of developing mental retardation secondary to late diagnosis of infantile hypothyroidism. CCH is frequently associated with other pituitary defects causing life-threatening situations (like e.g. adrenocorticotropic hormone deficiency) which could benefit from the early detection of CCH, avoiding considerable morbidity and mortality. CCH is not easy to identify clinically, and therefore few children are investigated for the disorder. The current knowledge on the genetic bases of CCH is also scarce. At the hypothalamic level no gene defects causing CCH have yet been identified in humans, but pituitary (thyrotrope)-selective genes encoding the TSH-releasing hormone (TRH) receptor (TRHR), the TSH β-subunit (TSHB) and, recently, the immunoglobulin superfamily factor 1 (IGSF1) are genes involved in isolated central hypothyroidism. Moreover, central hypothyroidism is a complex condition where many regulatory signals are implicated and converge to finely modulate the activity of the hypothalamic-pituitary-thyroid axis. This review focuses on novel pathogenic mechanisms and their implications to understand human CCH and improve the identification and the therapeutic handling of this elusive disease in the pediatric age.

Thyroid hormone cell membrane transport defect.

In the last few years, many studies have pinpointed the crucial role of thyroid hormone (TH) transporters for TH action in human target cells. The importance was better documented by the phenotype observed in patients harboring mutations of the monocarboxylate transporter 8 (MCT8) gene immediately linked to Allan-Herndon-Dudley syndrome, in which severe neurological findings are associated with abnormal TH levels. The hereditary pattern of MCT8 mutations is X chromosome linked, with males presenting a homogeneous neurological psychomotor phenotype and mental retardation associated with low serum thyroxine and elevated triiodothyronine levels. The mechanism of disease is still obscure, and the physiopathology as well as the existent therapeutic options need to be discussed in order to improve the clinical management.

Neonatal screening and a new cause of congenital central hypothyroidism.

Congenital central hypothyroidism (C-CH) is a rare disease in which thyroid hormone deficiency is caused by insufficient thyrotropin (TSH) stimulation of a normally-located thyroid gland. Most patients with C-CH have low free thyroxine levels and inappropriately low or normal TSH levels, although a few have slightly elevated TSH levels. Autosomal recessive TSH deficiency and thyrotropin-releasing hormone receptor-inactivating mutations are known to be genetic causes of C-CH presenting in the absence of other syndromes. Recently, deficiency of the immunoglobulin superfamily member 1 (IGSF1) has also been demonstrated to cause C-CH. IGSF1 is a plasma membrane glycoprotein highly expressed in the pituitary. Its physiological role in humans remains unknown. IGSF1 deficiency causes TSH deficiency, leading to hypothyroidism. In addition, approximately 60% of patients also suffer a prolactin deficiency. Moreover, macroorchidism and delayed puberty are characteristic features. Thus, although the precise pathophysiology of IGSF1 deficiency is not established, IGSF1 is considered to be a new factor controlling growth and puberty in children.

Acute hypophysitis and hypopituitarism in early syphilitic meningitis in a HIV-infected patient: a case report

BackgroundSexually transmitted diseases and most notably syphilis-infections are rising amongst men who have sex with men. In HIV-co-infected patients, an accelerated clinical course of syphilis neurological involvement is known.Case presentationA 46 year old HIV-positive male patient came in to our emergency department in the late evening with acute fever, rapidly progressive cephalgia and photophobia. Palmar skin efflorescence was evocative of an active syphilis infection. A reactive Treponema pallidum particle agglutination (TPPA) assay with positive Treponema pallidum-specific IgG/IgM immunofluorescence as well as a highly reactive Veneral diseases research laboratory (VDRL) test confirmed the diagnosis. Liquor pleocytosis, liquor protein elevation and a highly positive VDRL test in cerebrospinal fluid (CSF) were interpreted in context of the clinical symptoms as neurosyphilitic manifestations within an early syphilis infection (stage II). Cranial nuclear magnetic resonance scans of the sella turcica, which were performed due to low thyroidea stimulation hormone (TSH) and thyroxin levels, showed signs of hypophysitis such as pituitary gland enlargement and inhomogeneous contrast enhancement. Advanced endocrine laboratory testing revealed hypopituitarism. Fourteen days of intravenous ceftriaxone treatment and levothyroxine- and hydrocortisone-substitution led to complete disappearance of all clinical symptoms. Two months later, nuclear magnetic resonance scan showed normal pituitary size and that the syphilis serology had normalized.ConclusionWe report to the best of our knowledge the first case of a HIV-positive patient with acute hypophysitis and hypopituarism due to early neurosyphilis infection. Ceftriaxone treatment and levothyroxine- and hydrocortisone-substitution led to the disappearance of all clinical symptoms. We strongly recommend to exclude syphilis infection in every clinical situation unclear in HIV-patients, especially when additional risk factors are known.

Overweight increases risk of first trimester hypothyroxinaemia in iodine‐deficient pregnant women

Hypothyroxinaemia early in pregnancy may impair fetal brain development. Increased body weight has been associated with low thyroxine concentrations in non-pregnant women. In pregnant women, morbid maternal obesity is a risk factor for thyroid dysfunction. But whether lesser degrees of overweight that are much more common could be a risk factor for hypothyroxinaemia in pregnancy is unclear. The objective of this study was to investigate if overweight increases risk for thyroid dysfunction, and specifically hypothyroxinaemia, in iodine-deficient pregnant women. We performed a cross-sectional study at first hospital visit among healthy Thai pregnant women. We measured weight and height, urinary iodine concentration (UIC), serum thyroid hormones and thyroglobulin. Pre-pregnancy weight and relevant dietary factors were determined by questionnaire, and body mass index (BMI) was used to classify weight status. Among 514 women (mean gestational age, 11 weeks) with a median UIC of 111 μg dL(-1) , indicating mild iodine deficiency, 12% had low free thyroxine (fT4) concentrations: 3% had overt hypothyroidism; 7% had subclinical hypothyroidism; and 8% had isolated hypothyroxinaemia. Based on pre-pregnancy BMI, 26% of women were overweight or obese. In a multiple regression model, BMI was a negative predictor of fT4 (β = -0.20, P < 0.001). Compared to normal weight women, the prevalence ratio (95% CI) of a low fT4 in overweight women was 3.64 (2.08-6.37) (P < 0.01). Iodine-deficient pregnant Thai women who are overweight have a 3.6-fold higher risk of hypothyroxinaemia in the first trimester compared to normal weight women. Targeted screening should consider overweight a potential risk factor for thyroid dysfunction in pregnant women in iodine-deficient areas.

Lipid Profile and Some Hormonal Disorders in Serum of High-Fat Diet Fed Rats

Background: Chronic consumption of high-fat diet (HFD) induces obesity. The purpose of the current study was to evaluate the impact of high-fat diet-induced obesity on lipid profile and levels of certain hormones in male albino rats. Material and Methods: A total of forty two 12-week old male albino rats were divided into three groups: control group fed a normal diet, obese group I fed 25% HFD and obese group II fed 50% HFD. Each group was divided into two subgroups (seven rats for each) feeding on the corresponding diet for four and eight weeks. Serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-Chol), low density lipoprotein cholesterol (LDL-Chol), free Triiodothyronine (FT3), free Thyroxine (FT4), Insulin, Leptin and Adiponectin were assessed at the end of 4 th and 8 th weeks. Also LDL/HDL-cholesterol ratios of control and obese groups were calculated at the same time intervals. Results: The obtained results indicated significant increase in all parameters of serum lipid profiles in addition to elevation of the LDL/HDL-cholesterol ratios of obese rats compared to those of the controls. In response to HFD, marked increase was recorded in the levels of insulin and leptin while values of FT3 and adiponectin were reduced significantly. On the other hand, HFD did not change the levels of FT4. Most of the recorded changes were more obvious by increasing either the percentage of fats or the feeding period. Conclusion: In conclusion, HFD induces some hormonal disorders accompanied by disturbance of the lipid profile.

Consumptive hypothyroidism in an Egyptian baby with benign neonatal hemangiomatosis: a case report

IntroductionBenign neonatal hemangiomatosis is a condition in which multiple cutaneous hemangiomas appear at birth or shortly thereafter; visceral complications are absent. Here, we report a case of a consumption hypothyroidism in an Egyptian baby with benign neonatal hemangiomatosis.Case presentationAn 8-month-old Egyptian boy with benign neonatal hemangiomatosis was referred to our institution for evaluation of developmental delay. Initial examination revealed a quiet baby who was able to sit only with support. He had hypotonia, a large anterior fontanelle, puffy eyes, cold extremities, hypothermia, bradycardia, and abdominal distension. An examination of his skin revealed more than 100 dome-shaped red-purple cutaneous hemangiomas that varied in size from 5 to 10mm on the back, the abdomen and the extremities without mucus membrane involvement. He had low serum free thyroxine concentration and triiodothyronine levels and high thyroid-stimulating hormone and reverse-triiodothyronine levels. A work-up that involved appropriate imaging ruled out visceral involvement. Based on the above mentioned data, a diagnosis of consumptive hypothyroidism due to benign neonatal hemangiomatosis was made. He was started on oral thyroid medication which was gradually increased to 90μg L-thyroxine daily (15μg/kg/day). After three months of treatment, he was able to sit alone without support and he had normal levels of thyroid-stimulating hormone and serum free thyroxine.ConclusionThyroid function should be assessed periodically in babies with benign neonatal hemangiomatosis, especially if symptoms of hypothyroidism appear or the size and number of hemangiomatosis increase rapidly. Moreover, high doses of L-thyroxine may be needed to achieve euthyroidism during the infancy.

Congenital Hypothyroidism

Congenital Hypothyroidism

Recurrent spontaneous ovarian hyperstimulation secondary to hypothyroidism in an adolescent girl

Ovarian hyperstimulation syndrome (OHSS) is characterized by ovarian enlargement due to multiple ovarian cysts and a fluid shift into the extravascular space [1]. Some forms of OHSS have reportedly occurred during spontaneous pregnancy such as multiple pregnancies and associated conditions including, hypothyroidism, polycystic ovary syndrome, and follicle-stimulating hormone receptor (FSHr) mutations [2–4]. This report describes a case of recurrent OHSS associated with hypothyroidism in an adolescent girl with a non-remarkable family history and normal FSHr. An 18-year-old adolescent girl was admitted to our hospital with symptoms of abdominal pain and distension. Transabdominal ultrasonography (USG) showed mild ascites and bilateral ovarian multilocular cysts extending into the midabdomen. The results of blood counts and electrolyte analyses were normal. The hormonal evaluation revealed undetectable human chorionic gonadotropin (hCG), normal follicle-stimulating hormone (FSH) (6.5 IU/L) and luteinizing hormone (LH) (9.2 IU/L), high estradiol (E2) (4.000 mIU/mL) and thyroid-stimulating hormone (TSH) (100 lU/mL; normal range 0.47–5 lU/mL), and low free thyroxine (4.5 pmol/L; normal range 11–24 pmol/L). Abdominal magnetic resonance imaging (MRI) showed massively enlarged bilateral multicystic structures of presumable bilateral ovarian origin extending into the midabdomen (Fig. 1). Pituitary MRI was normal. Conservative medical management comprising was considered due to the presence of moderate spontaneous OHSS. Oral thyroxine (levothyroxine at 100 lg/day) was instituted on the basis of hypothyroidism. Abdominal symptoms were relieved with the beginning of menstruation within 2 weeks. Four months later, the patient presented to our center with similar symptoms. USG findings were similar to bilateral multilocular cysts in both ovaries and mild ascites. Serum hormonal analysis revealed a higher E2 level (10.000 mIU/mL) with a high TSH (20 lU/mL) and normal free thyroxine (15 pmol/L). Blood counts and electrolyte analyses were normal. Observation and supportive medical treatment was considered. The patient was discharged after 10 days with complete resolution of all clinical symptoms. Oral thyroxine reached a dose of 200 lg/day. Hormonal tests for thyroid function were normal 2 months after her second admission and the ovarian cysts completely regressed after 6 months. Bidirectional DNA sequencing of the FSHr gene was performed by PCR amplification to rule out FSHr abnormality in this case. No differences in the DNA sequence in the 10 exons were observed between the wild-type FSHr gene and those obtained from the patient. The exact mechanism underlying the relationship between OHSS and hypothyroidism is not clearly understood. One explanation of this rare association is that TSH has weak FSH activity on mutated FSHr, causing ovarian stimulation [5]. Another explanation is based on the release of FSH and LH by low levels of thyroid hormones, in addition to the targeted activation of TSH release. This seemed to be the cause in our case as FSHr sequencing was normal. In the literature, all the reported recurrent form of O. Erol (&) H. Ayik A. U. Derbent Department of Obstetrics and Gynecology, Antalya Research and Education Hospital, 07050 Antalya, Turkey e-mail: dronurerol@hotmail.com

Endocrine Evaluation of Children with and without Shwachman-Bodian-Diamond Syndrome Gene Mutations and Shwachman-Diamond Syndrome

To characterize the endocrine phenotype of patients with Shwachman-Diamond syndrome (SDS). Clinically indicated endocrine screening data from 43 patients with SDS or SDS-like presentation were analyzed according to sex, age, and genetic testing. In addition to 25 patients with biallelic Shwachman-Bodian-Diamond syndrome (SBDS) gene mutations, we evaluated 18 patients with cytopenias who were receiving pancreatic enzyme replacement but were without SBDS mutation. We performed a retrospective review of growth records and clinically indicated endocrine evaluations. Of patients with SBDS mutations, 2 had low stimulated growth hormone levels, 2 had mildly elevated thyrotropin levels, 5 had abnormal glucose levels, and 1 had an elevated follicle-stimulating hormone level (post transplantation). In contrast, 1 patient without SBDS mutations had postprandial hyperglycemia and 3 had mildly low free thyroxine levels without short stature. Endocrine abnormalities were identified in 19% of short patients and 26% of the whole group. Of patients with SBDS mutations, 56% had a height expressed in SD units from the mean for age and sex of <-1.8, in contrast to only 12% of patients without SBDS mutations (38% of the whole group). Body mass index z score was significantly greater in the group with SBDS mutations (P<.001). Although short stature was more common in patients with SBDS mutations, no consistent endocrine phenotype was observed in patients with SDS regardless of genetic testing.

Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years

Introduction:Primary hypothyroidism is one of the most frequent complications observed in-patients suffering from thalassemia. We investigated and reviewed the thyroid function in all thalassemic patients attending the Pediatric Endocrine Clinic of Hamad Medical Center, Doha, Qatar during the last 10 years of follow-up.Patients and Methods:A total of 48 patients with ί-thalassemia major between 5 years and 18 years of age. Thyroid dysfunction was defined as follows: Overt hypothyroidism (low Free thyroxine [FT4] and increased thyroid-stimulating hormone [TSH] levels >5 μIU/ml); subclinical hypothyroidism (normal FT4, TSH between 5 μIU/ml and 10 μIU/ml) and central (secondary) hypothyroidism (low FT4 and normal or decreased TSH).Results:A total of 48 patients (22 males and 26 females) completed a 12 year-period of follow-up. During this period, hypothyroidism was diagnosed in 17/48 (35%) of patients. There was no significant difference in the prevalence in males 7/22 (32%) versus females 10/26 (38%). Sixteen of the patients had hypothyroidism after the age of 10 years (94%). The prevalence of overt hypothyroidism had risen from 0% at the age of 7 years to 35% at the age of 18 years. None of the patients had high anti-thyroperoxidase antibody titers. Out of 17 patients, 13 patients with hypothyroidism had normal or low TSH level (not appropriately elevated) indicative of defective hypothalamic pituitary response to low FT4 (central hypothyroidism). Three patients (6.3%) had subclinical hypothyroidism (TSH between 5 uIU/ml and 10 uIU/ml and normal FT4). The general trend of FT4 level showed progressive decrease over the 12 years, whereas, TSH levels did not show a corresponding increase. These data suggested defective hypothalamic pituitary thyroid axis involving both TSH and FT4 sretion in patients with thalassemia major over time. There was a significant negative correlation between serum ferritin and FT4 (r = −0.39, P = 0.007), but no correlation was found between ferritin and TSH.Conclusions:Worsening of thyroid function was observed in 35% of the studied thalassemic patients by the age of 18 years. The lack of proper increase of TSH in response to the low circulating levels of FT4 in 13/17 (76%) of these patients indicates a relatively high incidence of defective pituitary thyrotrophic function in these patients.

Role of Bamboo-Shoot in the Pathogenesis of Endemic Goiter in Manipur, North East India

Endemic goiter is prevalent in the iodine-sufficient region of Manipur, India. Bamboo shoot (BS), a goitrogenic plant food, are consumed regularly in the area. The objective of this study was to examine the role of BS in the pathogenesis of endemic goiter. Goiter prevalence, urinary iodine, and thiocyanate (SCN) excretion in school children, iodine content in drinking water, and the household consumption of salt fortified with iodine were measured. To confirm the goitrogenic potential of BS, its progoitrogenic constituents were fed to rats as part of an iodine-sufficient diet, after which the animals' thyroid gland morphology and functional status were assessed. Goiter prevalence was 31% in 4852 children, and the median urinary I and SCN levels were 176.3 μg/L and 0.962 ± 0.190 mg/dL, respectively. Of the households assessed, 90% consumed salt fortified with adequate iodine. Progoitrogenic constituents were high in BS from Manipur. Increased thyroid weight, hypertrophy and hyperplasia of follicular cells, decreased thyroid peroxidase activity, and low serum thyroxine (T4) and triiodothyronine (T3) levels were observed in BS-fed rats. Nearly one third of the studied participants had palpable goiter, despite a successful salt iodine fortification program. SCN from BS causes goiter in iodine-sufficient experimental animals. Similar ingestion in study participants was confirmed and is the likely cause for the persistence of endemic goiter in the Manipur region.

Evaluation of autonomic functions in subclinical hypothyroid and hypothyroid patients.

Background:Autonomic dysfunction may contribute to cardiovascular morbidity in subclinical hypothyroid patients. It is controversial whether the abnormality exists in sympathetic or the parasympathetic function. It is also not known whether the severity of autonomic dysfunction is related to the degree of thyroid deficiency.Design of Study:Prospective case control.Materials and Methods:Autonomic functions based on heart rate (HR) and blood pressure (BP) responses to various maneuvers were evaluated and scored in twenty two subclinical hypothyroid patients, 30-50 years and compared with twenty hypothyroid patients. Biochemical estimation of TSH, fT3, fT4, TPO antibody was done.Result:Sympathetic function abnormalities were seen in 82% subclinical hypothyroid patients and 85%hypothyroid patients when one test was abnormal. Parasympathetic dysfunction was also recorded in eight patients in both groups. When two abnormal tests were used as the selection criteria sympathetic function abnormality was observed in about 41% subclinical hypothyroid and 65% hypothyroid patients. There were no intergroup differences in autonomic functions, score and TPO levels. The TSH levels were not related to type or degree of autonomic dysfunction. Systolic BP in both groups and diastolic BP in hypothyroid patients were higher with lower thyroxine levels but the patients were normotensive.Conclusion:Autonomic dysfunction of comparable degree was seen in subclinical hypothyroid and hypothyroid patients. Sympathetic function abnormality was more common although decreased parasympathetic function reactivity was also present. These abnormalities were unrelated to TSH levels.

Hoffmann’s syndrome and pituitary hyperplasia in an adolescent secondary to Hashimoto thyroiditis

Diffuse muscle hypertrophy is a rare complication of acquired hypothyroidism. When accompanied by stiffness, weakness, and painful muscle cramps, the condition is known as Hoffmann's syndrome (HS). HS is usually seen in young adults due to long-standing untreated primary hypothyroidism. We report a very rare case of HS with muscle hypertrophy and pituitary hyperplasia complicating hypothyroidism in an adolescent. A 12-year-old male admitted with muscle pain, headache, and fatigue. He had marked hypertrophy of both calf and shoulder muscles. Laboratory tests indicated elevated muscle enzymes and lipids with an elevated thyrotropin and low thyroxine levels. Hashimoto thyroiditis was confirmed on thyroid studies. He had also papilledema bilaterally and magnetic resonance imaging showed an enlargement of the pituitary gland. Treatment with thyroid hormone resulted in complete improvement of symptoms within 3 months. HS is a rare but treatable form of acquired myopathies and can be seen in children due to untreated hypothyroidism. All patients with an acquired myopathy and muscular pseudohypertrophy should be screened regarding thyroid hormones.

1346 Hypothyroxinemia vs Hypothyroidism in Very Low Birth Weight Infants

Transient hypothyroxinemia without elevated thyroid-stimulating hormone (TSH) levels is common in prematurity, especially in very-low-birth weight (VLBW) infants. The transient hypothyroxinemia of prematurity (THOP) has been seen as a “benign”...