Laboratory Evidence Of Hypothyroidism Research Articles

ODP504 PERICARDIAL EFFUSION AS A LIKELY CONSEQUENCE OF NON-COMPLIANT MANAGEMENT OF HYPOTHYROIDISM

Abstract Hypothyroidism is a well-known cause of pericardial effusion with an incidence of about 3-27%. If not diagnosed in time it can lead to potentially serious complications, such as cardiac tamponade leading to hemodynamic instability. It should be considered as a causative or exacerbating agent in any patient presenting with pericardial effusion and known, suspected or laboratory evidence of hypothyroidism, e. g., elevated TSH or reduced serum free T4. We present a case of a 50-year-old woman with a Past Medical Hx of hypertension, intermittently insulin-treated type 2 diabetes for 20 years, coronary artery disease, and hypothyroidism with medical non-compliance, and s/p right BKA. She initially presented to an outside hospital for altered mental status (specifically, inability to follow simple commands and orientation only to self). She was transferred to this facility for evaluation of limb ischemia. She was agoitrous with no reported palpable thyroid abnormalities. Her admission chest x-ray exhibitedan enlarged cardiac silhouette. Her initial serology was significant for a serum TSH of 178 uIU/mL (NL: 0.45-5.33 uIU/mL), FreeT4 <0.25 ng/dl (NL: 0.58-1.64 ng/dl),Free T3 1.65 pg/mL (NL: 2.5-3.9 pg/mL), andhighly elevated anti-thyroglobulin and anti-peroxidase antibodies. She was diagnosed as having primary hypothyroidism secondary to Hashimoto's thyroiditis. She was re-started on levothyroxine (L-T4) at a dose of 150 mcg on day 1, which was reduced to 100 mcg daily on days 2-4 but readjusted to 125 mcg daily on days 5-8 and 150 mcg daily thereafter. During the 25 th day of admission in the Rehabilitation unither serum TSH showed a gradual decline from 178 to 22 prior to discharge. Her Free T4 increased to 1.18 and her Free T3 increased to 2.24 by discharge. Her pericardial effusion was managed by placement of a pericardial window. Pericardiocentesis yielded over 600 ml of clear serous fluid (protein content 5.1 gm/dl) without evidence of malignancy, infection or inflammation. This case highlights the importance of not only recognizing the diagnosis of hypothyroidism but of assessing the duration and adequacy of its management. Likewise, an enlarged cardiac silhouette in this setting should be considered as possibly representing a pericardial effusion and impending source of a cardiac tamponade. Presentation: No date and time listed

Association of TSH Levels in the Therapeutically Neglected Range of 6.5–8 mIU/L with Significant Changes in Liver and Kidney Function: A Retrospective Study of the Kashmiri Population

Background: The thyroid gland secretes hormones crucial for growth, differentiation, regulation of metabolic processes, and homeostasis. In response to underactivity of this gland, the pituitary secretes thyrotropin, also known as the thyroid-stimulating hormone (TSH). Medication for thyroid hypofunction is usually started when TSH levels exceed 10 mIU/L. However, we hypothesize that TSH levels much below this therapeutic threshold level may herald significant renal and hepatic dysfunction. The present study was thus conducted to assess liver and kidney function parameters in cases having TSH in the subclinical range with particular focus on the therapeutically neglected (6.5–8 mIU/L) range.
 Methods: Hospital laboratory archives of 297 adults with laboratory evidence of hypothyroidism, that is, TSH > 6.5 mIU/L, were retrieved and compared with data obtained from 430 euthyroid hospital controls, that is, TSH < 2.5 mIU/L, also from the same period. The thyroid profile and clinical chemistry analyses were performed on Beckman Coulter’s UniCel DxI 800 and AU 5800, respectively. SPSS version 20 was used to analyze the results.
 Results: Significant differences in triiodothyronine (T3), thyroxine (T4), TSH, urea, creatinine, total bilirubin, total protein (TP), and liver enzymes were observed between cases with TSH > 6.5 mIU/L and controls (P < 0.05). There was also a significant difference in T4, TSH, urea, creatinine, total bilirubin, albumin and aspartate aminotransferase (AST) among cases with TSH in the range of 6.5–8 mIU/L when compared with controls (P < 0.05). A correlation of T3 with TSH, urea, and creatinine was seen (P < 0.05). No correlations between TSH and other clinical chemistry parameters could be observed. However, in the 6.5–8 mIU/L subgroup, correlation of TSH was seen with TP and albumin only.
 Conclusion: Authors found that, as a rule, subtle renal and hepatic dysfunction were established in cases with TSH levels <8 mIU/L, which was below the typical “therapeutic cut-off” of 10 mIU/L. Accordingly, we advocate against incautiousness and suggest regular monitoring, especially in the 6.5–8 mIU/L range.

Comparative Study of Calculated LDL-Cholesterol Levels with the Direct Assay in Patients with Hypothyroidism.

Background Hypothyroidism is one among the many factors that predisposes one to coronary artery disease. As low-density lipoprotein-cholesterol (LDL-C) is associated with cardiovascular risk, calculated LDL-C should have good accuracy with minimal bias. Hypothyroidism alters the lipid composition of lipoproteins by the secretion of triglyceride-rich lipoproteins, which affects the calculation of LDL-C. The present study aimed to compare 13 different formulae for the calculation of LDL-C including the newly derived Martin's formula by direct assay in patients of hypothyroidism. Method In this analytical cross-sectional study, a total of 105 patients with laboratory evidence of hypothyroidism, from January to June 2019, were studied, and blood samples were subjected for lipid profile analysis at central biochemistry laboratory. Calculated LDL-C was assessed by different formulae. Result We observed that calculated LDL-C by Friedewald's, Cordova's, Anandaraja's, Hattori's, and Chen's formulae has bias less than ± 5 compared with direct LDL-C, with Anandaraja's formula having the lowest bias (2.744) and Cordova's formula having lowest bias percentage (-1.077) among them. According to the Bland-Altman plots, the bias in Friedewald's and Anandraja's were equally distributed below and above the reference line of direct LDL-C. Conclusion This is the first study comparing different formulae for LDL-C calculation in patients with hypothyroidism. Anandaraja's formula was as equally effective as Friedewald's formula when used as an alternative cost-effective tool to evaluate LDL-C in hypothyroid patients. The recently proposed Martin's formula for calculated LDL-C had a higher bias when compared with Friedewald's and Anandaraja's formulae in patients with hypothyroidism.

An Integrative Approach to Common Behavior and Learning Problems in Children: A Role for Gluten Sensitivity and MTHFR Polymorphism

An integrative approach to chronic health problems was applied to 43 patients within a pediatric practice over a period of 24 months. Symptoms included chronic headache syndromes, abdominal symptoms, fatigue, and some with behavioral or learning problems. Among these patients were 12 children with a diagnosis of attention deficit hyperactivity disorder (ADD/ADHD) whose parents were seeking either to avoid the use of stimulant medication or seek an alternative to prescribed treatment. Evaluation included a careful nutritional/dietary history, questionnaire for symptoms of gluten sensitivity (GS), and in select cases, laboratory evaluation for thyroid function, GS, and genetic analysis for methylenetetrahydrofolate reductase (MTHFR) polymorphism.Among the large group of children, of 15 screened for MTHFR polymorphism, 14 were positive. Of nine children with a history of ADD/ADHD, 8 were positive. Of 43 children with a history suggesting possible GS, 32 were found to have elevated antigliadin IgG antibodies. This included 10 of the 12 children with a diagnosis of ADD/ADHD. One child on stimulant treatment for ADHD was found to have laboratory evidence of hypothyroidism with tissue resistance to thyroid hormone, and thyroid function normalized and markedly elevated reverse T3 dropped substantially after discontinuation of stimulant treatment for 8 weeks.Clinical experience here supports the idea that among children with chronic health problems that include a behavioral or learning component, consideration of possible GS, genetic polymorphism for MTHFR, and thyroid function may be appropriate.

Pneumocystis jiroveci thyroiditis: report of 15 cases in the literature

The authors review the epidemiology, clinical manifestations, diagnosis and treatment of Pneumocystis jiroveci thyroiditis of 15 cases reported in the medical literature. Patients with acquired immunodeficiency disease syndrome were particularly at risk. P. jiroveci thyroiditis was diagnosed at autopsy as a part of disseminated infection in a substantial number of patients without clinical manifestations and laboratory evidence of thyroid dysfunction. Local signs and symptoms of infection were indistinguishable from other infectious thyroiditis and included neck enlargement with or without cervical pain, sometimes associated with dysphagia and dysphonia, and clinical and laboratory features of hypothyroidism. Antemortem diagnosis of fungal thyroiditis was made by direct microscopy and culture of a fine-needle aspirate in most cases. As most patients with P. jiroveci thyroiditis had disseminated Pneumocystis infection with a delay in diagnosis and treatment, the overall mortality was high. Pneumocystis jiroveci thyroiditis is rare but should be suspected in HIV-infected patients with CD4 count lower than 200 cells micro(-1) on prophylatic inhalatory pentamidine who present with neck enlargement with or without pain, and clinical and laboratory evidence of hypothyroidism.

Isquemia miocárdica reversible en el hipotiroidismo: comunicación de un caso

A silent, reversible myocardial ischemia with normal coronary angiography and reversible with thyroid hormone substitution, has been recently described in hypothyroid patients. We report a 49 years old male with an abnormal exercise electrocardiogram detected in a preventive medical examination. He had laboratory evidence of hypothyroidism and a history of two years of asthenia and progressive coarsening of the voice. The Thallium myocardial perfusion study, showed an alteration of coronary flow during exercise in the septum and lower wall of the left ventricle. Thyroid hormone substitution was started and three months later, a coronary angiography was normal. After six months a repeated Thallium perfusion study and exercise electrocardiogram were informed as normal.

Acute Myocarditis in Fulminant Systemic Sclerosis

Myositis and myocarditis have been reported in progressive systemic sclerosis, and these patients have had favorable therapeutic responses to intravenous pulse methylprednisolone. Thus far, premortem biopsy documentation of myocarditis and myocardial fibrosis has not been reported in such patients. We report the case of a patient with subacute congestive heart failure six months after she developed Raynaud's phenomenon. Clinical examination was typical of scleroderma but there was no proximal muscle weakness. She had elevated creatine kinase and MB-creatine kinase and laboratory evidence of hypothyroidism. Echocardiogram demonstrated four-chamber dilatation and severe left ventricular dysfunction. Cardiac catheterization revealed normal epicardial coronary arteries and severely decreased cardiac index. A skin biopsy specimen of the forearm was consistent with diffuse systemic sclerosis, and an endomyocardial biopsy specimen demonstrated mild fibrosis and lymphocytic infiltrate. Her heart failure initially improved with digoxin, furosemide, and enalapril. She also received L-thyroxine and intravenous methylprednisolone. The heart failure progressed over the next six weeks and she died. Patients with scleroderma and new-onset heart failure may have acute myocarditis.

Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells.

The development of a goiter and hypothyroidism in a 28-year-old man in whom metastatic melanoma had been treated with interleukin-2 and lymphokine-activated killer cells (LAK cells) prompted us to assess thyroid function in patients undergoing this therapy. Thirty-four patients with advanced neoplasms who had received interleukin-2 and LAK cells were followed for at least four weeks after treatment. Seven patients (21 percent) had laboratory evidence of hypothyroidism, with a decline in the serum thyroxine concentration to below normal (less than or equal to 35 nmol per liter; normal, 65 to 148), a decline in the serum free thyroxine index, and a rise in the serum thyrotropin concentration (peak values, 7.2 to 166 mU per liter; normal, 0.5 to 5.5) 6 to 11 weeks after treatment. Two patients had elevated serum thyrotropin levels before treatment, which increased further after treatment. In two patients, these abnormal values returned to normal within 10 months. All five symptomatic patients had borderline or elevated serum antimicrosomal antibody titers after treatment; two had serum antibodies to thyroglobulin. Five of the seven patients with hypothyroidism (71 percent) but only 5 of the 27 euthyroid patients (19 percent) had evidence of tumor regression (P less than 0.02). None of 11 patients treated with interleukin-2 but not LAK cells had hypothyroidism. We conclude that treatment with interleukin-2 and LAK cells can cause hypothyroidism, possibly by exacerbating preexisting autoimmune thyroiditis, and that it may be associated with a favorable tumor response.

MINIMAL THYROID INSUFFICIENCY(MTI) IN CHILDREN WITH CONSTITUTIONAL DELAYED GROWTH(CDG)

Therapeutic trial c thyroid preparation in absence of clinical & laboratory evidence of hypothyroidism has been reported in children c short stature. (J.Ped. 80,988,72). Patients c MTI have normal T3,T4,& TSH levels but an augmented TSH response to TRH. (Peak TSH response > 20uIU/ml). TSH & T3 response to TRH was assessed in 20 children (mean age 11.7 range 7.9-15.8 yrs ♂ 18: ♀ 2) c CDG. TRH test was done with IV bolus TRH 4ug/kg/BW. after an overnight fast of 10 hrs. 5 had augmented TSH response (Gr.B) 15 had normal (Gr.A). There was no significant difference in basal levels of T3,T4,free T4 & TSH. Mean TSH reponse was significantly higher at all times in Gr.B vs Gr.A T3 % increase was lower in Gr.B 29.1±2.5(N3) vs Gr.A 41.9±4.0(N9) p < 0.05. Augmented TSH response & lower T3 % increase in response to TRH was found in 25% of children c CDG. This could be an evidence of minimal thyroid insufficiency or of hypothalamic pituitary thyroid dysfunction in children c CDG. Treatment c thyroxine in two patients for 5 months showed 140% increase in annual growth rate. Controlled therapeutic trial is indicated.

The consequences of inappropriate treatment because of failure to recognize the syndrome of pituitary and peripheral tissue resistance to thyroid hormone

Since the description of the syndrome of global (peripheral tissues and pituitary) resistance to thyroid hormone, new cases are being recognized with increasing frequency. The patient described herein had a markedly elevated serum TSH concentration of 260 μU/mL at the time of diagnosis. Studies suggest that elevations of serum TSH levels in this and other patients with the syndrome are most likely iatrogenic in origin. The patient was 3 1 2 years old when a goiter and a high serum T 4 concentration were detected. Despite subtotal thyroidectomy, antithyroid drugs were required to maintain her T 4 level in the normal range. She was referred at age 11 1 2 years because of recurrent goiter. Her parents and five older siblings had normal thyroid function. Off therapy, her serum T 4 level was 14.9 μg/dL, FT 4I was 17.0, T 3 was 362 ng/dL, TSH was 260 μU/mL, and antibodies were negative. There were no signs of thyrotoxicosis, her bone age was 7 years, her growth was stunted (third percentile), her intellectual quotient (IQ) was 67, and there was a 30–50 dB sensorineural hearing loss. The presence of a pituitary adenoma was ruled out. Her TSH had normal bioreactivity and rose to 540 μU/mL in response to TRH. Triiodothyronine was given in incremental doses of 50, 100, 200, and 400 μg/d over 28 days. The log concentrations of serum TSH showed an inverse linear correlation with serum T 3. While receiving the highest dose of T 3, on which the level of serum T 3 ranged from 1400 to 2500 ng/dL, the TSH response to TRH normalized (basal 4.2 and peak 20 μU/mL), as did the high levels of serum cholesterol, carotene, and T 4. Her BMR rose from +5 to +22%, her IQ rose to 77, and she gained weight without an increase in caloric intake. Only minimal changes were observed in levels of urinary cAMP, hydroxyproline, magnesium, and nitrogen. All values, with the exception of the weight gain, returned to baseline 2 months after T 3 treatment was discontinued. The TSH level was suppressed by l-dopa and by prednisone. Long-term therapy with equivalent doses of T 4 (from 300 to 1000 μg/d) produced a growth of 3 cm during the initial 6 weeks, 10.5 cm over the ensuring year (above the 10th percentile), and regression of goiter without thyrotoxicosis. The patient exhibited resistance to thyroid hormone in pituitary and peripheral tissues. The optimal dose of T 4 replacement could be predicted by studying tissue responses to incremental doses of T 3. The marked elevation in serum TSH concentration, stunted growth, and laboratory evidence of hypothyroidism were due to the limited thyroidal reserve caused by thyroidectomy. All patients with an impaired ability to compensate for the defect as a result of inappropriate treatment should be given thyroid hormone in amounts short of producing catabolic effects. Such a dose is expected to normalize the basal serum TSH concentration and its response to TRH.

292 HYPERBILIRUBINEMIA AND IDIOPATHIC HYPOPITUITARISM IN THE NEWBORN PERIOD

The association between neonatal hypopituitarism and liver dysfunction with prolonged jaundice has been made. We describe two patients who presented with severe neonatal hypoglycemia (HG), hepatomegaly, and hyperbilirubinemia (direct and indirect). There was clinical and laboratory evidence of hypothyroidism, hypo-adrenalism, hypogonadism and growth hormone (GH) deficiency in both. Case 1 (female) had 4 blood exchange transfusions. Liver enzymes were slightly elevated and bilirubin levels returned to normal within 5 months. A liver biopsy showed mild portal inflammation. Growth rate (GR) was 50% of normal during the first 6 mo. in the absence of demonstrable GH release. Somatomedin(SM) levels were 50% of normal childhood levels at 3 mo. but decreased to hypopituitary levels thereafter. SM increased 3.5 fold and GR was 80% of normal after GH treatment was added to T4 and cortisol replacement therapy. Case 2 (male) had grossly abnormal liver function tests, required 1 blood exchange transfusion and hyperbilirubinemia lasted for 8 mo. A liver biopsy revealed giant cell hepatitis. Despite T4 and cortisol therapy, hypoglycemic episodes continued until GH treatment was begun at 2½ yrs. Vigorous treatment of HG and early diagnosis of hypothyroidism and hypoadrenalism are crucial for a successful outcome. HG enhances the production of unconjugated bilirubin, but this can only partially explain the observed liver dysfunction in neonatal pan-hypopituitarism where T4 and GH deficiency likely also play a role.

Serum thyrotropin and thyroid hormone levels in humans receiving chronic potassium iodide.

Serum thyroxine (T4), triiodothyronine (T3) and thyrotropin (TSH) concentrations were measured in 13 patients with chronic obstructive pulmonary disease receiving saturated solution of potassium iodide (SSKI). All had a low serum T4 and a high serum TSH concentration. However, serum T3 levels were normal in eight. Recovery of normal thyroid function was observed in each of the seven patients in whom the iodide was discontinued. The same hormones were measured in four normal subjects who received 30 drops of SSKI daily for 11 weeks. An increase in serum TSH levels was preceded by a fall in serum concentrations of T4 and to some extent, T3. Upon SSKI withdrawal subsequent increases in the serum concentrations of both thyroid hormones, but particularly T3, resulted in the return of serum TSH to baseline levels. None of the subjects developed clinical hypothyroidism. It is not apparent why the normal subjects did not exhibit clinical or laboratory evidence of hypothyroidism while the patients with chronic pulmonary disease did. A younger age and the shorter duration of iodide administration in the normal subjects may have played a role.

Effects of amiodarone on thyroid function in patients with ischaemic heart disease.

Thyroid function was evaluated clinically and biochemically in 12 patients with ischaemic heart disease receiving 200 mg oral amiodarone three times daily for periods up to 6 weeks. During drug administration, no patient developed clinical or laboratory evidence of hypothyroidism, but serum levels of T3 tended to fall and those of T4 increased but not to levels outside the normal range. Amiodarone produced a significant reduction in heart rate with prolongation of the QTc interval of the electrocardiogram without altering either the PR interval or the QRS duration. These effects of the drug were still present 4 weeks after cessation of treatment. In spite of the high iodine content, amiodarone does not, therefore, depress thyroid function to any important degree during chronic administration and its antianginal action does not appear to be caused by the production of generalized hypothyroidism.

Iodine and lithium-induced hypothyroidism: Documentation of synergism

Signs and symptoms of hypothyroidism were noted in a patient receiving lithium carbonate for 2 years as prophylaxis against recurrence of mania and depression. When lithium therapy was stopped, the hypothyroidism resolved; but it recurred with the administration of potassium iodide. When potassium iodide therapy was discontinued, the patient became euthyroid. In a second patient chemical evidence of hypothyroidism (fall in circulating thyroid hormone levels, elevation of serum thyrotropin) was noted after he had received 3 weeks of lithium therapy. With the addition of potassium iodide, laboratory evidence of hypothyroidism became more pronounced, and clinical signs of hypothyroidism developed. All abnormalities resolved promptly following the withdrawal of lithium and iodine. These observations suggest that lithium and iodine can act synergistically to produce hypothyroidism and that the combined use of these agents should be avoided.

Thyroid in the treatment of short stature

Therapeutic trials with thyroid were undertaken in ten short children, despite the absence of clinical or laboratory evidence of hypothyroidism, on the premise that response to treatment is the ultimate criterion of thyroid status. Eight of the ten experienced an acceleration of growth; this may be interpreted as reflecting a placebo effect or it is possible that thyroid function tests may not identify all children who would respond to treatment.

Endemic Cretinism in Goiaz, Brazil

Twenty-six endemic cretins were studied in the middle west of Brazil, an endemic goiter region. Goiter was found in 18 patients and deaf-mutism in 10. Clinical and laboratory evidence of hypothyroidism was present in 2 cases. In all others the determination of the 24-hr I131 thyroid uptake and PBI127 gave normal results. A positive serum (low titer) for antithyroglobulin auto-antibodies (TRC test) was found in only one cretin. The clinical appearance of the patients conformed to the descriptions in classic papers on endemic cretinism. All the cretins showed characteristic neurologic signs: oligophrenia, generalized hyperreflexia, spasticity and loss of muscular strength in the lower limbs. In 10 patients we performed electroencephalograms and observed diffuse anomalies; no abnormalities were observed on pneumoencephalograms in 6 cretins. The pathogenesis of endemic cretinism is discussed.

Effect of Hypothyroidism on Antidiuretic Action of Pressor Principle of Posterior Pituitary

The effects of total ablation of the normal thyroid gland in man on the action of injected adrenalin and of insulin have been reported previously., Studies of the effect of total thyroidectomy on the action of injected pressor principle of the posterior lobe of the pituitary are presented below. The antidiuretic effect, and blood pressure and heart rate following the subcutaneous injection of pitressin have been studied. Several observations support the idea that the thyroid gland is a factor in maintaining water balance. Whether the antidiuretic action of pitressin is altered after thyroidectomy has not been established. We have compared the effect of pitressin in postoperative hypothyroidism with its effect in subjects with normal thyroid function. Studies were made in 3 subjects with normal thyroid function, in 3 subjects with clinical and laboratory evidence of hypothyroidism which developed after total thyroidectomy, and in 1 additional subject both before operation and subsequently when hypothyroidism had developed. The elapsed time between operation and the pitressin studies varied from 1 to 9 months. Thyroidectomy in 2 of the 4 patients operated was performed for the relief of congestive heart failure, in the other 2 for angina pectoris, in accord with considerations outlined elsewhere by Blumgart and his associates., The basal metabolic rates of the 4 hypothyroid patients studied ranged between —19 and —36% and averaged —27%, clinical signs varying from those of mild hypothyroidism to rather marked myxedema were present. The antidiuretic effect of pitressin in each instance was evaluated by studying the urine output after a liter of water, both on a control day and on a day when pitressin was administered. The following regimen of study was utilized: at 7:00 A. M., the patient received a standard light breakfast with no coffee or added salt. At 9:00 A. M., with the patient in the recumbent position, blood pressure and heart rate measurements were made at 5-minute intervals until constant readings were obtained. The patient then emptied his bladder, and either 0.10 or 0.15 cc. of pitressin was administered subcutaneously, the site of injection being massaged. (On the control day pitressin was omitted.) The patient then ingested 1000 cc. of water. The urine voided between 9 A. M. and 2:00 P. M. was collected at hourly intervals: the volume, specific gravity, and chloride content of the 5 specimens were measured. The chloride contents of the urine were measured by the method of Folin. Blood pressure and heart rate measurements were made every 15 minutes for the first hour following pitressin injection, and at 1 1/2 and 2 hours after injection. The results were compared with those obtained on a control day. Basal metabolic rate measurements were made with a Benedict-Roth apparatus, the results being calculated with reference to the Aub-DuBois normal standards.