Chronic Hypothyroidism Research Articles

Triggers of stress cardiomyopathy and their association with clinical outcomes

Abstract Background Stress cardiomyopathy can be a result of physical stress, emotional stress, or both. Whether the type of trigger affects clinical outcomes is not well studied. Purpose The objectives of this study were to identify the prevalence of emotional and physical stressors and to assess differences in patient characteristics and mortality based on the type of trigger. Methods We conducted a retrospective review of 523 consecutive patients who presented to our institution from 2006 to 2016. All patients presented with acute coronary syndrome. Triggers for stress cardiomyopathy were abstracted from reviewing patients' medical records. Patients were categorized into those with 1) physical trigger, 2) emotional trigger, 3) both physical and emotional trigger, or 4) no known trigger. Baseline characteristics and clinical outcomes were reported. Results Among 523 patients with stress cardiomyopathy, 151 (28.9%) had a physical trigger, 189 (36.1%) had an emotional trigger, 30 (5.7%) had both physical and emotional triggers, and 153 (29.3%) had no known triggers identified. Men comprised the higher proportion of patients with physical triggers. Comorbidities including diabetes, pulmonary disease, chronic kidney disease and hypothyroidism were more prevalent among patients with physical triggers. Compared to patients with no obvious triggers, patients with a physical trigger had a much higher mortality rate (hazard ratio 2.0, 95% CI 1.2–3.3, p=0.007), whereas patients with an emotional trigger had significantly lower mortality (hazard ratio 0.40, 95% CI 0.21–0.89, p=0.007). Conclusion Different triggers for stress cardiomyopathy is associated with different baseline characteristics and clinical outcomes. Overall survival is worst in the group with an identified physical trigger. Figure 1 Funding Acknowledgement Type of funding source: None

Transient Hypothyroidism During Lactation Alters the Development of the Corpus Callosum in Rats. An in vivo Magnetic Resonance Image and Electron Microscopy Study.

Magnetic resonance imaging (MRI) data of children with late diagnosed congenital hypothyroidism and cognitive alterations such as abnormal verbal memory processing suggest altered telencephalic commissural connections. The corpus callosum (CC) is the major inter-hemispheric commissure that contra-laterally connects neocortical areas. However, in late diagnosed neonates with congenital hypothyroidism, the possible effect of early transient and chronic postnatal hypothyroidism still remains unknown. We have studied the development of the anterior, middle and posterior CC, using in vivo MRI and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI) treated rats were studied. One group, as a model for early transient hypothyroidism, was MMI-treated from postnatal day (P) 0 to P21; some of these rats were also treated with L-thyroxine (T4) from P15 to 21. Another group modeling chronic hypothyroid, were treated with MMI from P0 to 150 and from embryonic day 10 to P170. The results obtained from these groups were compared with same age control rats. The normalized T2 signal obtained using MRI was higher in MMI-treated rats and correlated with a low number and percentage of myelinated axons. The number and density of myelinated axons decreased in transient and chronic hypothyroid rats at P150. The g-ratio (inner to outer diameter ratio) and the estimated conduction velocity of myelinated axons were similar between MMI-treated and controls, but the conduction delay decreased in the posterior CC of MMI-treated rats compared to controls. These data show that early postnatal transient and chronic hypothyroidism alters CC maturation in a way that may affect the callosal transfer of information. These alterations cannot be reversed after delayed T4-treatment. Our data support the findings of neurocognitive delay in late T4-treated children with congenital hypothyroidism.

SAT-514 Nivolumab Related Primary Hypothyroidism: 3 Years of Follow-Up

BACKGROUND: Primary hypothyroidism is one of the most common endocrinopathies related to the use of nivolumab, a monoclonal antibody against the immune checkpoint molecule programmed death-1 (PD-1). The long-term course of this condition, especially after the completion of nivolumab treatment, has not been widely reported.CLINICAL CASE: A 70-year-old man presented with weight gain despite poor appetite, cold intolerance, and constipation. He noticed these symptoms after receiving the first three months of treatment with nivolumab for renal cell carcinoma. His heart rate was 66, blood pressure was 130/79 mm Hg, and body mass index was 28.3. The thyroid gland was normal-sized without palpable nodules, deep tendon reflexes were normal, and cardiac and pulmonary exams were unremarkable. Laboratory test results were consistent with primary hypothyroidism: thyroid-stimulating hormone (TSH) was elevated at 97.11 mIU/L (normal, 0.35-4.70 mIU/L), and total thyroxine was less than 1 mcg/dL (normal, 4.5-12.0 mcg/dL). Both anti-TPO antibody (222.6 IU/ml, normal<5.6 IU/ml) and anti-thyroglobulin antibody (10.6 IU/ml, normal <4.1 IU/ml) levels were elevated. There was no prior history of thyroid disease; two of the patient’s sisters had chronic hypothyroidism. Treatment with levothyroxine resulted in rapid resolution of symptoms. With dose titration of levothyroxine over the course of a few months, the patient achieved biochemical euthyroidism. Nivolumab therapy was continued for more than two years, during which a stable levothyroxine dose was maintained, and the patient remained clinically and biochemically euthyroid. Ultimately the renal cell carcinoma was determined to be in remission, and nivolumab therapy was stopped. Subsequently, the anti-TPO antibody titer was observed to have returned to the normal range (2.3 IU/ml). However, as of five months following discontinuation of nivolumab, and 32 months since the onset of thyroid dysfunction, the patient’s hypothyroidism persists as reflected by non-suppressed TSH values on levothyroxine treatment.CONCLUSION: We have observed the course of nivolumab-induced primary hypothyroidism over almost three years in an individual patient. The hypothyroidism has persisted, requiring ongoing levothyroxine replacement at a dose of approximately 1.4 mcg/kg daily. An interesting feature of this case is the disappearance of anti-TPO antibody positivity after discontinuation of nivolumab. We speculate that the ongoing hypothyroidism despite the absence of detectable autoantibodies may be related to progressive thyroid cell apoptosis. Further long-term observations will determine whether permanence of nivolumab-induced hypothyroidism is the rule.

Open Surgical Thrombectomy and Coronary Stent Placement for Treatment of Aortic Thrombotic Disease in a Bitch

Background: The thrombotic aortic disease in dogs and cats is characterized by the pathological formation of blood clots that can rupture and obstruct the blood flow. Abdominal ultrasonography can identify the location and extension of thrombus in the main vasculature and using the doppler it is possible to observe the blood flow around the thrombus. Stents are expandable tube-shaped endoprosthesis characterized as a metal mesh and used to prevent or repair stenoses, allowing liquid, gas, or solids to flow. This report aims to describe the surgical and medical treatment of aortic thrombotic disease followed by coronary stents placement in a bitch.Case: An 8-year-old Shih Tzu bitch, presented for evaluation of a 1-month progressive hind limbs paresis. Nociception was present in both limbs, but the patient presented discomfort and vocalization when manipulating the pelvic limbs. A complete blood count demonstrated anemia, mild neutrophilia, and lymphopenia. Serum biochemistry found an increase in ALT, ALP, blood urea nitrogen, and CK. Abdominal ultrasonography detected mild bulging of the caudal aorta and trifurcation of the iliac arteries. Increased intraluminal echogenicity and absence of blood flow were also detected using duplex doppler. The initial medical treatment was ineffective in improving clinical signs, therefore surgical repair was performed. The aorta was isolated and clamped with Satinsky forceps and incised. The thrombus fragmented during removal. A non-compliant high-pressure balloon was used to dilated and remove small fragments of blood clots from the right and left external iliac arteries. Coronary stents of 32 mm length by 2.75 mm diameter were placed to keep both iliac arteries free. Immediately after the procedure, there was a detectable distal pulse in both hind limbs. Despite intensive medical treatment, the patient evolved to respiratory distress and died on the sixth day after surgery. At necropsy, there were thrombi in the lumen of the arteries and several organs in addition to a large hyaline thrombus occluding 80-90% of the aortic lumen and left femoral artery. In the trifurcation region, clots were present, and stents placed in the iliac arteries were also occluded.Discussion: The occurrence of aortic and iliac thrombosis is associated with several conditions, including neoplasia, chronic kidney disease, heart failure, gastric dilatation-volvulus, hypothyroidism, and hyperadrenocorticism (HAC). In this case, the underlying cause of thromboembolism was supposed to be related to an endocrine condition, since the patient had clinical signs compatible with HAC; however, the low-dose dexamethasone suppression test was borderline and further examination could not be afforded. The diagnosis of thrombosis at the iliac trifurcation was obtained through ultrasonographic examination. Computed tomographic and nuclear resonance imaging could have been applied as well. The medical management of the thromboembolic disease was based on anticoagulant therapy with both heparin and clopidogrel in association with surgical thrombectomy and coronary stents placement. Despite the efforts, the patient died shortly after the surgical procedure, which was expected since high rates of mortality and morbidity is often related to the thromboembolic ischemia. The necroscopic examination of the animal found thrombi at the stents, cranial aorta, and microscopically in several tissues. The failure to directly treat the cause of the thrombus, which could not be diagnosed in time, may negatively interfered in patient survival time. The thrombectomy and coronary stents placement reestablished the femoral pulse immediately after surgery, which has been reported in other studies. The surgical resolution of aortic thrombus should be addressed in further studies.

MON-347 Bilateral Adrenal Hemorrhage in a Patient with Myelodysplastic Syndrome and Clostridium Difficile Infection

Background: Acute primary adrenal insufficiency due to bilateral adrenal hemorrhage is an often-missed diagnosis, which can lead to shock and death if untreated. Risk factors include anticoagulation, hypercoagulable states, trauma, and sepsis. Clinical Case: A 67-year-old female with myelodysplastic syndrome (MDS), maintained on lenalinomide and periodic blood transfusions, presented with progressive nausea, vomiting, diarrhea, posterior chest pain, and dyspnea. Her medical history also included chronic hypothyroidism. She was afebrile with normal pulse and blood pressure, and no abnormalities on cardiac, pulmonary, or abdominal exams. The WBC count was 6.0 K/mm3 (baseline, < 4.0 K/mm3), hemoglobin was 7.5 g/dL, and platelets 497 K/mm3. Electrolytes were normal except for potassium of 3.0 mEq/L. PT was not prolonged. TSH was normal. There was no evidence for pulmonary embolism on chest CT scan. She was admitted for suspected gastroenteritis, and started on IV fluids, analgesics, antiemetics, and enoxaparin. On hospital day 3 the patient developed fever and disorientation, and was started on broad antibiotics. Several hours later, she became hypotensive, and received fluid boluses. The hemoglobin fell to 6.7 g/dL and sodium decreased to 132 mEq/L, with potassium remaining low at 3.1 mEq/L. The following day sepsis developed, with tachycardia, tachypnea, persistent fever, and recurrent hypotension. CT scan of the abdomen, ordered to rule out an occult abscess, revealed colitis and bilateral adrenal hemorrhages, and PCR for C. difficile in the stool returned positive. Immediately following a cosyntropin stimulation test, hydrocortisone 100 mg every 8 hours was started; the post-cosyntropin cortisol level returned at 3.8 mcg/dL. Oral vancomycin treatment was initiated. Over the following 24 hours the patient’s status improved, with normalization of blood pressure and mental status. Tests for other bacterial, viral, and fungal infections returned negative. The patient’s diarrhea improved, and she was discharged home on hospital day 10. The hydrocortisone had been tapered to 50 mg daily in divided doses, with plans to continue tapering as an outpatient, and eventually to re-test adrenal axis function. Conclusions: We present a patient with MDS who developed C. difficile colitis leading to sepsis, complicated by adrenal insufficiency due to bilateral hemorrhages. Individuals with MDS may have dysfunctional platelets and neutrophils, which may have increased the risks for bleeding and infection in this case; other risk factors for C. difficile infection were absent. The brief use of enoxaparin may also have been a predisposing factor. This report adds to the few cases in the literature of adrenal hemorrhages in the setting of MDS, and underscores the importance of maintaining a high index of suspicion for this rare complication with protean manifestations.

First Korean case of a STAT1 gene mutation: chronic mucocutaneous candidiasis, hypothyroidism, chronic hepatitis and systemic lupus erythematosus

First Korean case of a <i>STAT1</i> gene mutation: chronic mucocutaneous candidiasis, hypothyroidism, chronic hepatitis and systemic lupus erythematosus

Increase in the constrictor effects of Rho-kinase in skeletal muscle and coronary arteries of rats with chronic hypothyroidism

Aim. The deficit of thyroid function is known to be accompanied by an increase in the overall peripheral vascular resistance. This work tested the hypothesis that long-term hypothyroidism leads to an increase in the vasoconstrictor effect of Rho-kinase in skeletal muscle and heart resistance arteries of adult rats.Materials and methods.Male Wistar rats consumed the antithyroid drug propylthiouracil (PTU) in drinking water (0.025%), starting at 10 weeks of age. The rats of the control group received PTU-free water. After 14 weeks, the contractile responses of the gastrocnemius muscle arteries (to the α1-adrenoceptor agonist methoxamine) and the septal coronary artery (to the thromboxane A2 receptor agonist U46619) were isometrically recorded. The contribution of the Rho-kinase to the arterial contractile responses was assessed using inhibitor Y27632 (3 μM).Results.The consumption of propylthiouracil was accompanied by a marked decrease of thyroid hormone concentrations and an increase in total cholesterol serum level as well as a decrease in body weight. Maximal contractile responses of studied arteries were also reduced in hypothyroid rats. However, basal tone and reactivity to the moderate concentrations of agonists in arteries of hypothyroid rats were increased compared to control animals. Y27632 significantly weakened the contractile responses of the arteries and negated the differences between the two groups of rats.Conclusion.Chronic hypothyroidism leads to an increase in the activity of the Rho-kinase signaling pathway in the arteries of the gastrocnemius muscle and heart, which results in the increase of the spontaneous tone of the arteries and their reactivity to agonists.

Transient Hypothyroidism During Lactation Arrests Myelination in the Anterior Commissure of Rats. A Magnetic Resonance Image and Electron Microscope Study.

Thyroid hormone deficiency at early postnatal ages affects the cytoarchitecture and function of neocortical and telencephalic limbic areas, leading to impaired associative memory and in a wide spectrum of neurological and mental diseases. Neocortical areas project interhemispheric axons mostly through the corpus callosum and to a lesser extent through the anterior commissure (AC), while limbic areas mostly project through the AC and hippocampal commissures. Functional magnetic resonance data from children with late diagnosed congenital hypothyroidism and abnormal verbal memory processing, suggest altered ipsilateral and contralateral telencephalic connections. Gestational hypothyroidism affects AC development but the possible effect of transient and chronic postnatal hypothyroidism, as occurs in late diagnosed neonates with congenital hypothyroidism and in children growing up in iodine deficient areas, still remains unknown. We studied AC development using in vivo magnetic resonance imaging and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI) treated rats were studied. One group was MMI-treated from postnatal day (P) 0 to P21; some of these rats were also treated with L-thyroxine (T4) from P15 to P21, as a model for early transient hypothyroidism. Other rats were MMI-treated from P0 to P150 and from embryonic day (E) 10 to P170, as a chronic hypothyroidism group. The results were compared with age paired control rats. The normalized T2 signal using magnetic resonance image was higher in MMI-treated rats and correlated with the number and percentage of myelinated axons. Using electron microscopy, we observed decreased myelinated axon number and density in transient and chronic hypothyroid rats at P150, unmyelinated axon number increased slightly in chronic hypothyroid rats. In MMI-treated rats, the myelinated axon g-ratio and conduction velocity was similar to control rats, but with a decrease in conduction delays. These data show that early postnatal transient and chronic hypothyroidism alters AC maturation that may affect the transfer of information through the AC. The alterations cannot be recovered after delayed T4-treatment. Our data support the neurocognitive delay found in late T4-treated children with congenital hypothyroidism.

Prevalence of co-morbid conditions in Heart failure: an experience at tertiary care hospital

Introduction: Patients with heart failure (HF) have various co-morbidities that complicate management and may adversely affect outcomes. HF guidelines provide little discussion on this topic and evidence is sparse.Material and Methods: This is a descriptive cross-sectional study on 240 consecutive patients with HF admitted from September 2016 to July 2017 at B.P. Koirala Institute of Health Sciences (BPKIHS), Nepal. All patients admitted with diagnosis of HF with reduced or preserved ejection fraction (NYHA functional class III/IV) based on Framingham Criteria and echocardiography assessments were included. Pre-defined co-morbid conditions were assessed.Results: Mean age of patients was 53.5 years and 53% were female. Most patients were in NYHA class III or IV (25% and 75% respectively) and 28.3% had ischemia as a cause of HF. Among co-morbidities, 85% of patients with HF had at least one co-morbidity. Anemia (68.3%), coronary artery disease (30.4%), hypertension (26.6%), diabetes (18.7%) and chronic kidney disease (7.5%) were the co-morbidities with the highest prevalence. Chronic obstructive pulmonary disease (3.7%), sleep apnea (2.5%), hypothyroidism (2.5%) and stroke (2.5%) were less common. Of all patients, only 15% had no co-morbidity, 40% had one co-morbidity, 22% had two co-morbidities, and 13 % had three or more co-morbidities.Conclusion: Co-morbidities are common problems and anemia is the most common in our scenario which could be of multi-factorial etiology. Careful attention to the diagnosis and management of specific co-morbidities may help to improve outcomes in patients with HF. Journal of Nobel Medical CollegeVolume 6, Number 2, Issue 11 (July-December, 2017) Page:35-41

Rhabdomyolysis in a patient with chronic uncontrolled diabetes mellitus and hypothyroidism

Rhabdomyolysis is a syndrome characterised by muscle necrosis and dispersing its intracellular content in the circulation. Clinical symptoms are usually presented by muscle pain and muscle weakness. Rhabdomyolysis could be produced, among other causes, by diabetic ketoacidosis and hypothyroidism. We report a case of a 36 years old female patient who was admitted to the medical intensive care unit (MICU) because of rhabdomyolysis. At her admission we found compensated diabetic ketoacidosis with normal serum osmolarity and mild hypothyroidism. The patient was treated by rehydration, urine alkalinisation, forced augmentation of diuresis, correction of blood glucose levels, and levothyroxine substitution therapy. After 17 days, she was completely recovered and discharged home. We believe that rhabdomyolysis in our patient developed as a summary of two important factors, uncontrolled diabetes mellitus and hypothyroidism. Hypothyroidism, possibly fueled by bad regulate diabetes, may amplify the symptoms. Each considered factor separately may not be cause a muscle breakdown, but their combination can lead to serious and severe clinical symptoms associated with high levels of creatine kinase (CK) enzyme.

Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats

BackgroundThere is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The objective of the present study is to examine the consequences of chronic hypothyroidism, induced in adulthood, for the size of the ovarian follicle pool. In order to investigate this, adult female rats were provided either a control or an iodide deficient diet in combination with perchlorate supplementation to inhibit iodide uptake by the thyroid. Sixteen weeks later animals were sacrificed. Blood was collected for hormone analyses and ovaries were evaluated histologically.ResultsAt the time of sacrifice, plasma thyroid-stimulating hormone concentrations were 20- to 40-fold increased, thyroxine concentrations were negligible while tri-iothyronin concentrations were decreased by 40% in the hypothyroid group, confirming that the animals were hypothyroid. Primordial, primary and preantral follicle numbers were significantly lower in the hypothyroid ovaries compared to the euthyroid controls, while a downward trend in antral follicle and corpora lutea numbers was observed. Surprisingly the percentage of atretic follicles was not significantly different between the two groups, suggesting that the reduced preantral and antral follicle numbers were presumably not the consequence of increased degeneration of these follicle types in the hypothyroid group. Plasma anti-Müllerian hormone (AMH) levels showed a significant correlation with the growing follicle population represented by the total ovarian number of primary, preantral and antral follicles, suggesting that also under hypothyroid conditions AMH can serve as a surrogate marker to assess the growing ovarian follicle population.ConclusionsThe induction of a chronic hypothyroid condition in adult female rats negatively affects the ovarian follicular reserve and the size of the growing follicle population, which may impact fertility.

MANAGEMENT OF ENDOCRINE DISEASE: Hypothyroidism-associated hyponatremia: mechanisms, implications and treatment.

Patients with moderate to severe hypothyroidism and mainly patients with myxedema may exhibit reduced sodium levels (<135 mmol/L). The aim of this short review is the presentation of the mechanisms of hyponatremia and of the available data regarding its implications and treatment in patients with hypothyroidism. Hypothyroidism is one of the causes of hyponatremia, thus thyroid-stimulating hormone determination is mandatory during the evaluation of patients with reduced serum sodium levels. The main mechanism for the development of hyponatremia in patients with chronic hypothyroidism is the decreased capacity of free water excretion due to elevated antidiuretic hormone levels, which are mainly attributed to the hypothyroidism-induced decrease in cardiac output. However, recent data suggest that the hypothyroidism-induced hyponatremia is rather rare and probably occurs only in severe hypothyroidism and myxedema. Other possible causes and superimposed factors of hyponatremia (e.g. drugs, infections, adrenal insufficiency) should be considered in patients with mild/moderate hypothyroidism. Treatment of hypothyroidism and fluid restriction are usually adequate for the management of mild hyponatremia in patients with hypothyroidism. Patients with possible hyponatremic encephalopathy should be urgently treated according to current guidelines. Severe hypothyroidism may be the cause of hyponatremia. All hypothyroid patients with low serum sodium levels should be evaluated for other causes and superimposed factors of hyponatremia and treated accordingly.

Dietary-Induced Chronic Hypothyroidism Negatively Affects Rat Follicular Development and Ovulation Rate and Is Associated with Oxidative Stress1

The long-term effects of chronic hypothyroidism on ovarian follicular development in adulthood are not well known. Using a rat model of chronic diet-induced hypothyroidism initiated in the fetal period, we investigated the effects of prolonged reduced plasma thyroid hormone concentrations on the ovarian follicular reserve and ovulation rate in prepubertal (12-day-old) and adult (64-day-old and 120-day-old) rats. Besides, antioxidant gene expression, mitochondrial density and the occurrence of oxidative stress were analyzed. Our results show that continuous hypothyroidism results in lower preantral and antral follicle numbers in adulthood, accompanied by a higher percentage of atretic follicles, when compared to euthyroid age-matched controls. Not surprisingly, ovulation rate was lower in the hypothyroid rats. At the age of 120 days, the mRNA and protein content of superoxide dismutase 1 (SOD1) were significantly increased while catalase (CAT) mRNA and protein content was significantly decreased, suggesting a disturbed antioxidant defense capacity of ovarian cells in the hypothyroid animals. This was supported by a significant reduction in the expression of peroxiredoxin 3 ( ITALIC! Prdx3), thioredoxin reductase 1 ( ITALIC! Txnrd1), and uncoupling protein 2 ( ITALIC! Ucp2) and a downward trend in glutathione peroxidase 3 ( ITALIC! Gpx3) and glutathione S-transferase mu 2 ( ITALIC! Gstm2) expression. These changes in gene expression were likely responsible for the increased immunostaining of the oxidative stress marker 4-hydroxynonenal. Together these results suggest that chronic hypothyroidism initiated in the fetal/neonatal period results in a decreased ovulation rate associated with a disturbance of the antioxidant defense system in the ovary.

Psychiatric Disorders and Quality of Life in Patients with Hypothyroidism: A Narrative Review

Objective: To narrative review scientific articles that investigated psychiatric comorbidities and quality of life in patients with hypothyroidism. Method: A search was conducted in three databases; ISI Web of Science, Pubmed and PsycInfo; where 1333 references were found. After the exclusion of repeated and foreign language articles, restriction to the last ten years and analysis of titles and abstracts, 27 articles were chosen to compose this review. Results: Studies on patients with Thyroid disease; be it an excess or a deficiency of thyroid hormones, may produce psychiatric symptoms, in this instance the evidence of patients with anxiety and depression disorders is particularly noteworthy. The results of 14 studies selected for this review positively prove the association of the diagnostic with psychiatric disorders and quality of life. Conclusion: Although the searches were carried out for psychiatric comorbidities, anxiety and depression disorders were highly prevalent in the population with hypothyroidism. Other data of paramount importance was the emphasis on treatment blocking future developments in relation to emotional health, associated with chronic hypothyroidism, thereby establishing better quality of life in this population.

Effect of thyroid hormone replacement therapy on cognition in long-term survivors of aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a recently identified risk factor for chronic hypothyroidism. Patients with hypothyroidism often exhibit cognitive dysfunction. The aim of the present study was to determine the effects of thyroid hormone replacement therapy on cognition in aSAH survivors with hypothyroidism. A study population of 135 patients was recruited and subjected to the Montreal Cognitive Assessment (MoCA) and Beck Depression Inventory. Among the study population, 52 patients exhibited cognitive dysfunction. Thyroid hormone levels were measured in these patients using an electrochemiluminescence immunoassay in order to elucidate possible deficits in the thyrotrophic hormonal axes, and hypothyroidism was confirmed in 31 patients. Among these 31 patients, 22 patients consented to be randomized into groups and were administered levothyroxine replacement or a placebo treatment for 3 months. The MoCA and Wechsler Adult Intelligence Scale-Chinese version (WAIS-RC) testing were performed prior to and following the replacement therapy or placebo treatments. All subjects completed the study with no negative side effects. After 8-12 weeks of oral levothyroxine administration, it was observed that the serum concentration of thyroid-stimulating hormone was restored to normal levels. Furthermore, neuropsychological test results improved following the replacement therapy. A significant improvement was observed in the MoCA scores of the replacement group following therapy, with the exception of the score for abstraction. Additionally, significant improvements in the WAIS-RC were observed in the replacement group, with the exceptions of the information comprehension and letter-number sequencing scores. Thus, the present study has demonstrated the partial normalization of cognitive impairments in patients with hypothyroidism following aSAH as a result of appropriate levothyroxine replacement therapy.

Prematurity, smallness-for-gestational age and later hospital admissions: A nation-wide registry study

IntroductionBeing born premature or small for gestational age (SGA) is known to be associated with diseases later in life, such as gestational diabetes, hypertension and pre-eclampsia. In this study we examined the association between being born premature or SGA and all diseases diagnosed during hospital admissions later in life. MethodsUsing Danish nation-wide registries we created a cohort of 1,348,106 persons born 1974–1996 and assessed all unique diagnoses registered in the Danish Patient Registry (DPR) for hospital admissions in the period 1994–2007 (n=27,910,558). We determined the odds ratios for persons born premature or SGA using multivariate logistic regression. ResultsA total of 15,059 unique ICD‐10 diagnosis codes were represented in the period. Only diagnoses used at least 100 times were included in the analysis (n=4175). Of these 838 showed an odds ratio that was statistically significantly different from unity for people born premature or SGA. After correcting for multiple testing, 250 remained significant. The diagnoses covered diseases in most organ systems, including cardiovascular, endocrinological, infectious, neurological/neurosurgical, obstetric, orthopedic, psychiatric, lung & urological diseases, and occurred throughout childhood and early adulthood. Novel findings included increased risks for delayed puberty, neurofibromatosis type 1 and ileus and decreased risks of mononucleosis, peritonsillar abscesses, chronic hypothyroidism and several types of fractures and contusions later in life. ConclusionBeing born premature or SGA was associated with significantly altered risks of being admitted to a hospital with a wide range of diseases later in life, affecting almost all organ systems throughout childhood and early adulthood. Our findings may motivate testing in other cohorts and search for novel mechanisms of pathogenesis.

Subclinical hypothyroidism or thyroid autoimmunity and variant angina: by chance? Or with a chance?

Refer to the page 125-130 Proper functioning of thyroid is of importance due to its effects on the cardiovascular system.1),2) Furthermore, the relationship between hyperthyroidism and coronary vasospasm is well-known and has been continuously reported since the first description in a case report in 1979.3,4,5) The most important treatment of thyroid disease is the control of thyrotoxicosis and the majority of cases showed excellent outcomes after treatment of thyroid problems.5) While the relationship with hypothyroidism, including subclinical hypothyroidism, and coronary vasospasm has not been well-established until date, Nishikawa et al.6) reported their experience with variant angina in a patient of isolated adrenocorticotropin deficiency, inappropriate vasopressin secretion, and Hashimoto's thyroiditis. However, the patient had additional endocrine problems and the authors concluded that this variant angina was more related with the isolated adrenocorticotropin deficiency rather than Hashimoto's thyroiditis. In 1979, an earlier report demonstrated a case of variant angina that was well controlled with nitrate administration, and aggravated with the development of hypothyroidism and concurrent use of propranolol. Authors extrapolated aggravation of variant angina by working on beta blockers, which mediated alpha-mediated coronary artery spasm rather than treating hypothyroidism alone.7) Hence, it is complicated to search previous evidence regarding the effect of hypothyroidism or subclinical hypothyroidism on coronary artery vasospasm. Nonetheless, there is some theoretical background that demonstrates the possibilities of hypothyroidism or thyroid autoimmunity-mediated coronary artery vasospasm. Most commonly accepted mechanisms for coronary artery spasm include endothelial dysfunction and primary hyperactivity of vascular smooth muscle cells,8) and there are several articles that show endothelial dysfunction in hypothyroidism or subclinical hypothyroidism. Napoli et al.9) reported patients with acute hypothyroidism after surgical thyroidectomy or primary chronic hypothyroidism related to impaired endothelial and non-endothelial vasodilation. Moreover, recent data shows relation between subclinical hypothyroidism due to autoimmune thyroiditis and impaired endothelial dysfunction (both endothelium dependent and independent) and increased inflammatory markers in patients when compared to healthy volunteers.10) They concluded that low grade chronic inflammation may be one of the factors that contribute to endothelial dysfunction in subclinical hypothyroidism with autoimmunity. In this regards, KCJ, Lee et al.11) demonstrated relationship of autoimmunity, positive anti-thyroperoxidase (TPO) antibodies, and subclinical hypothyroidism to variant angina, which was confirmed by ergonovine provocation. Although the study lacked strong statistical correlation, it provides us with clinical implication that subclinical hypothyroidism or autoimmunity-related endothelial dysfunction might be presented as variant angina. However, studying compositions of thyroid function status in the subjects with positive anti-TPO antibodies may provide more accurate information, because of heterogeneity of positive provocation test group; including euthyroidism and subclinical hyperthyroidism. Definition of subclinical hypothyroidism is clear with high thyroid stimulating hormone (TSH) and normal free thyroxine (T4) levels. Other variations of hypothyroidism include low triiodothyronine (T3) syndrome (low T3 with normal TSH and free T4) and overt hypothyroidism (elevated TSH and low free T4). Anti-TPO antibodies are positive in 90% of Hashimoto's thyroiditis cases, 75% of Graves' disease cases, 10-20% of nodular goiter or thyroid carcinoma cases and even in 10-15% of normal individuals.12) Even though variant angina is frequently observed in real world practice and has been well-known for decades, there are still a number of mechanisms and trigger factors that remain to be solved.8) In the absence of definite evidences of relationship of overt hypothyroidism and coronary vasospasm, the weak relationship of subclinical hypothyroidism or thyroid autoimmunity including heterogeneous entities with coronary vasospasm can be considered. that the results come either by chance or with chance. The results may weaken the relationship between coronary vasospasm and thyroid dysfunction including hyperthyroidism and hypothyroidism, but it is clear that the results may be a trigger for future studies on clarifying the relationship between hypothyroidism and its variations, coronary vasospasm, and the effects of thyroid hormone on treatment of coronary vasospasm, especially with respect to medically intractable cases.

Editorial: New therapeutic targets for human placental angiogenesis disease.

Editorial: New therapeutic targets for human placental angiogenesis disease.

A Case Report on Autoimmune Polyendocrine SyndromeType 1

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autosomal recessive disorder characterized by autoimmune multiorgan dysfunction. The major components of APS type 1 are chronic mucocutaneous candidiasis,hypoparathyroidism and Addison’s disease.To establish this syndrome, at least two of these conditions have to be present. We report here one of such case, a 15-year old boy who presented with features of chronic mucocutaneous candidiasis, hypoparathyroidism, primary hypothyroidism,nail dystrophy and dental enamel hypoplasia that were consistent with APS-1.DOI: http://dx.doi.org/10.3329/jom.v15i1.19886 J Medicine 2014; 15: 98-101

Spectrum of Rheumatological Disorders: A Clinic-based Study

Ex vivo and in vitro studies of blood platelets were performed on a total of 70 clinically healthy donors of different age and sex and compared with the results observed in 86 patients suffering from venous thrombotic or arterial occlusive diseases (AOD) of the lower limb using several techniques. Significant thrombocytic hyperfunction present was found both nephelometrically and with the Wu and Hoak method in AOD. The nephelometrical data could be substantiated with the platelet-count-ratio (PCR) technique. The present studies demonstrate that all techniques available have serious limitations. Both the Wu and Hoak and the Born methods are incapable to reveal latent and abortive platelet dysfunctions. Pilot studies suggest that the resolution power of the nephelometric device can be augmented when platelet reactivity is increased by a "physiological" maneuver, namely by maximal body exercise of the subject to be examined, immediately before the aggregation test. It is emphasized that adherence to constant experimental conditions is a "conditio sine qua non" for comparative studies on platelet function.