High Incidence Of Hypothyroidism Research Articles

Thyroid Dysfunction in Patients with Chronic Hepatitis C Treated with Pegylated Interferon alpha Therapy

Purpose: Thyroid dysfunction has been reported in 1–3% of patients with chronic hepatitis C treated with interferon therapy. We prospectively studied this problem in our patients with an attempt to determine the role played by autoimmunity in thyroid dysfunction. Methods: 39 patients (18 males and 21 females) aged 18–55 years with chronic hepatitis C were treated with pegylated interferon alpha in combination with ribavirin. Baseline thyroid stimulating hormone (TSH) and free thyroxine (free T4) levels were obtained on all patients prior to therapy. At baseline, every patient had an autoimmune panel sent which consists of antithyroid microsomal antibody, antithyroglobulin antibody and thyroid stimulating immunoglobulins and was euthyroid prior to beginning interferon therapy. Beginning at week twelve all patients had TSH and free T4 levels monitored on a monthly basis for the duration of the therapy. If there was any variation from the normal range a new set of thyroid autoantibodies were redrawn to evaluate for development of autoimmune thyroid dysfunction. Results: 9 out of 39 patients (8 females and 1 male) or 23% showed changes in their thyroid functions between week 12 and the end of treatment. 7 of the 9 patients were genotype 3a.Of these group 8 patients became clinically hypothyroid and 1 patient developed transient hyperthyroidism requiring treatment and soon thereafter became hypothyroid requiring synthroid. From these 9 patients 2 developed new antithyroid microsomal antibodies and anti thyroglobulin antibodies while 1 patient showed increase in levels of preexisting microsomal and anti thyroglobulin antibody titers. 3 of the 9 patients or 33% had thyroid autoantibodies as the mechanism of hypothyroidism. Only 2 of the 9 or 22% developed new thyroid autoantibodies. Conclusions: In our cohort of mostly Pakistani genotype 3a patients there was a much higher incidence of hypothyroidism (23%) on PEG interferon and ribavirin treatment than 1–3%. This much higher rate of thyroid dysfunction could be due to a small sample size or it maybe due to a greater susceptibility of Pakistani women or genotype 3a patients to this complication. The large difference favors the latter. As the numbers show there is a 8 to 1 female predominance for this phenomenon. Finally only a minority of the cases are explained by thyroid autoantibodies (33%).This suggests that there are other unexplained mechanisms for the hypothyroidism perhaps including a direct effect of PEG interferon on the thyroid gland.

Thyroid Disorders in Hemodialysis Patients in an Iodine‐deficient Community

There are various changes in the thyroid gland and its function in chronic renal failure (CRF). These changes include lower levels of circulating thyroid hormone, altered peripheral hormone metabolism, decreased binding to carrier proteins, possible reduction in tissue hormone content, and increased iodine storage in the thyroid gland. The decrease of excretion of urinary iodine in CRF increases serum inorganic iodine level and iodine content of the thyroid, which consequently enlarges the gland. This study is designed to investigate the prevalence of goiter and thyroid dysfunction in patients with end-stage renal disease (ESRD) on hemodialysis (HD) in an iodine-deficient community. Eighty-seven (40 females and 47 males) HD patients and 169 (79 females and 90 males) healthy individuals as controls are included. Sex ratios for the patient and control groups are 0.85 and 0.88, respectively. Mean ages for the patient and control groups are 42.94 +/- 11.88 and 40.20 +/- 10.72 years, respectively. Examination of the thyroid gland using ultrasonography along with simultaneous measurement of blood levels of free-T4 (FT4), free-T3 (FT3), and thyrotropin (TSH) are made for every individual. The presence of goiter demonstrable by ultrasonography is found in 32.2% of the uremic patients and in 23.5% of the controls and its prevalence increases with age (P = 0.01). In 32 (36.8%) of the patients and 29 (17.1%) of the controls at least one thyroid nodule is found in ultrasonography. Between patients with or without a nodular goiter the authors could not observe any difference for duration of dialysis and serum levels of TSH, FT4, FT3, calcium, and albumin. In ESRD patients the prevalence of nodular goiter is higher for females (47.5% vs. 27.7%, P = 0.045) and increases with age (P = 0.04). Though incidence of hyperthyroidism is found to be similar for the two groups (1.14% in ESRD patients vs. 1.10% in controls), hypothyroidism is observed in 3.4% of ESRD patients but only 0.6% of controls. This high incidence of hypothyroidism and nodular goiter in ESRD patients shows that screening for thyroid dysfunction and goiter, using appropriate laboratory tests and ultrasonography, should be considered in evaluation of every ESRD patient.

Hormone levels associated with immune responses among inhabitants in HLNRAs of Ramsar-Iran

The purpose of this study was to determine whether the exposure to HLNR affects the hormone levels associated with immune responses in young and elderly subjects. The studies demonstrated a decreased level of DHEA and increased level of cortisol in the elderly HLNRA group which might be possibly associated with higher cumulative doses. There was a higher incidence of hypothyroidism in the HLNRA group, mostly in elder group. A significant increase of CD69 expression on CD4+ T lymphocytes was found in the young HLNRA group. Low levels of DHEA in the elder group were correlated to their increased IgE levels.

Hypothyroidism secondary to radiation and chemotherapy in pediatric Hodgkin's Disease

8532 Background: Hypothyroidism in pediatric Hodgkin's disease (HD) survivors is reported due to neck irradiation (RT). An effect of chemotherapy remains controversial. Methods: Records of 467 newly diagnosed HD patients treated on different regimens between 1979 and 2002 were reviewed. Radiation dose to the neck and clinical features were recorded. Hypothyroidism was defined as a TSH > 4.7 or need for thyroxine therapy. The cumulative incidence of hypothyroidism was calculated using SAS version 8.2 and treating relapse, death, or second cancer as competing risks. Results: Of 457 evaluable patients, 261 (57%) were male, 378 (83%) white; median age was 15.2 years (range 3 –21.7) and median time of thyroid follow up was 4.5 years (range 0.1 to 22.3). Treatment regimens used during this period were COPP, COPP/ABVD, VAMP, VEPA, VAMP/COP or Stanford V combined with RT or RT alone in selected patients with localized disease. The Table shows the cumulative incidence of hypothyroidism at 5 and 10 years according to the RT dose given. Patients in Group1 had no RT, a 7% incidence of hypothyroidism, and served as the reference group. Comparison of Group3 and Group4 shows a significant difference in cumulative incidence of hypothyroidism (p=0.004). Age at treatment was not a risk factor for developing hypothyroidism. The relative risk for females compared to males of developing hypothyroidism was 1.6 (p=0.0002) while the relative risk for blacks of developing hypothyroidism was 0.36 (p=0.0015) compared to non-blacks.Conclusions: Chemotherapy added to moderate (21–26.9Gy) dose RT, resulted in a higher incidence of hypothyroidism than high dose RT (>27Gy) alone. Table: Hypothyroidism Cumulative Incidence according to Radiation Dose / Chemotherapy No significant financial relationships to disclose.

Perioperative pain: opioids: Naloxone use in postoperative pain management

Concerns have been raised by groups such as the Institute for Safe Medication Practices that overaggressive pain management has led to an alarming increase in fatal respiratory depression events. In 2001, of the 199 medication related sentinel events reported to the Joint Commission, 21% involve opioids. The administration of naloxone may be an important monitor of the quality and safety of postoperative pain management. However, studies supporting the use of naloxone as a quality measure are absent. The purposes of this study are to determine incidence and factors associated with naloxone administration in the postoperative setting and to critically examine naloxone as a potential quality measure. Subjects included all postoperative adult inpatients at an academic hospital who received naloxone and an equal number of matched control patients who did not receive naloxone during the calendar year 2003. Real time medical record audits were performed to examine patient demographics, relevant medical history, postoperatively administered analgesics and central nervous system depressants, documented sedation and respiratory assessments, reason provided for naloxone administration, and patient outcome. Preliminary results (as of 9/30/03) indicate that 0.68% (44/6436) of all adult inpatient postop patients received naloxone. Patients who received naloxone were significantly older (61 yrs vs. 48), had lower respiratory rates (12.66/min vs. 14.54), higher sedation scores (3.59/6 vs. 2.59), and lower pulse oximetry (86.38 vs. 95.26) than matched controls. In addition, naloxone recipients received more CNS depressants, had higher incidence of hypothyroidism, renal dysfunction, and sleep apnea, and were treated less often with epidural anlagesia than control patients. There was no significant difference in the amount of opioids taken by the two groups. Reversal of excessive opioid sedation was the primary reason provided for naloxone administration, however 25% (11/44) of the patients were later determined to have new diagnosis which contributed to the need for naloxone.

Hypothyroidism in children with medulloblastoma: a comparison of 3600 and 2340 cGy craniospinal radiotherapy

Purpose : To determine if low-dose craniospinal irradiation (2340 cGy) with chemotherapy is associated with a lower incidence of hypothyroidism compared to standard dose (3600 cGy) with or without chemotherapy in children with medulloblastoma. Patients and Methods : Between 1980 and 1999, 32 patients ≤20 years old survived after craniospinal irradiation with or without chemotherapy. Twenty patients received 3600 cGy craniospinal irradiation (CSI), whereas 12 had 2340 cGy CSI; all patients received a posterior fossa boost to a total dose 5040–5580 cGy. The median ages at the time of CSI for those receiving 2340 cGy and 3600 cGy were 7.2 and 10.2 years, respectively. Chemotherapy (CT) was employed in 22 children. All children who received 2340 cGy had CT consisting of vincristine, CCNU, and either cisplatin or cyclophosphamide. Ten of 20 (50%) patients receiving 3600 cGy had CT; the most common regimen was vincristine, CCNU, and prednisone. Serum-free thyroxine and thyroid-stimulating hormone concentrations were measured in all children at variable times after radiotherapy. Thyroid-stimulating hormone responses to i.v. thyrotrophin-releasing hormone were assessed in those suspected of having central hypothyroidism. Median follow-up for children receiving 2340 cGy was 5 years (range: 2–11.2 years), whereas for those receiving 3600 cGy, follow-up was 12.5 years (range: 2.4–20 years). Results : Eighteen patients (56%) developed hypothyroidism at a median time after radiotherapy of 41 months (range: 10 months to 18 years). Primary hypothyroidism was more common than central hypothyroidism (38% and 19%). All 7 children <5 years developed hypothyroidism, whereas 9 of 15 (60%) ages 5–10 and 2 of 10 (20%) age >10 years had hypothyroidism ( p < 0.001). Hypothyroidism was documented in 10 of 12 (83%) who had 2340 cGy + CT, 6 of 10 (60%) who had 3600 cGy + CT, and 2 of 10 (20%) who had 3600 cGy without CT ( p < 0.025). Conclusions : Current treatment regimens consisting of chemotherapy and 2340 cGy craniospinal irradiation followed by a posterior fossa boost for medulloblastoma do not show a reduction of hypothyroidism. Young age and use of chemotherapy were associated with a higher incidence of hypothyroidism.

Sonographic diagnosis and grading of Hashimoto's thyroiditis.

There is no ideal test for the diagnosis of Hashimoto's thyroiditis (HT). The purpose of this study was to determine the type of information sonography provides in these patients. In 47 cases of HT we identified four distinct sonographic patterns which correlated with degree of disease severity. The higher patterns had larger glands, higher antithyroid antibody titers, lower T4 and higher TSH levels, and higher incidence of hypothyroidism. With sonography we were able to suspect the diagnosis in patients with goiter of unknown etiology, to measure gland size, identify patients with functional impairment, and predict which patients required treatment. No other single test provides so much information in patients with HT.

Reduced affinity for thyroxine in two of three structural thyroxine-binding prealbumin variants associated with familial amyloidotic polyneuropathy.

T4-binding prealbumin (TBPA), a protein synthesized by the liver, circulates as a tetramer and transports 15-20% of T4. We studied 3 variants of the TBPA monomer recently identified in serum and amyloid fibrils of patients affected by familial amyloidotic polyneuropathy (FAP). They represent single amino acid substitutions at positions 30 (type I), 60 (Appalachian), and 84 (type II). Tests of thyroid function and the apparent association constant (Ka) of T4 binding to TBPA were measured in whole serum from 14 carriers of FAP identified clinically, by amino acid sequence analysis, or by DNA restriction fragment analysis. Significant reduction of Ka was found in subjects with FAP types I and II, but not in subjects with the Appalachian type. Mean (+/- SD) values of 0.24 +/- 0.08 X 10(7) M-1 for type I and 0.26 +/- 0.10 X 10(7) M-1 for type II were significantly (P less than 0.0001) lower than those for normal relatives (1.39 +/- 0.30 X 10(7) M-1) or unrelated normal subjects (1.41 +/- 0.18 X 10(7) M-1). The mean Ka value for the five subjects with FAP of the Appalachian type was slightly but not significantly reduced (1.08 +/- 0.11 X 10(7) M-1). There was no overlap of individual Ka values of subjects with types I and II TBPA with those of subjects from all other groups. Abnormalities of thyroid function included slight but significant reductions of the mean total serum T4 concentration in the subjects with type II FAP and the mean serum total T3 concentration in those with type I FAP. Four subjects with FAP (two type II and two of the Appalachian type) had biochemical evidence of hypothyroidism. The three subjects with total serum T3 levels below the limit of normal had amyloid cardiomyopathy. These results indicate that TBPAs from subjects with FAP types I and II have relatively lower affinity for T4. Although none of the substituted amino acids in these variant TBPAs contribute directly to the surface of the putative T4-binding site, the side chains of amino acids 30 and 84, but not 60, interact with internal residues of the beta-structure which forms the presumed binding site, in agreement with our results of Ka measurements. The high incidence of hypothyroidism is due to the probably fortuitous occurrence of Hashimoto's thyroiditis as well as to partial destruction of the thyroid gland by amyloid deposits.

Pyrophosphate arthropathy: a study of metabolic associations and laboratory data.

105 consecutive patients with pyrophosphate arthropathy have been studied. Disease associations and metabolic abnormalities were compared with those of an age and sex matched group of 105 acute medical admissions, and with 48 patients presenting with uncomplicated osteoarthritis. Patients with pyrophosphate arthropathy had a higher incidence of hypothyroidism (10, hyperparathyroidism 92), and chronic steroid therapy (15) than did those in the comparative groups. Laboratory data showed abnormalities suggesting chronic inflammatory disease in many patients, but no other unexpected metabolic findings. Metabolic abnormalities were uncommon in pyrophosphate arthropathy, and extensive metabolic screening of patients was unrewarding.

Thyroid abnormalities associated with treatment of malignant lymphoma.

The effects on the thyroid of radiation therapy to the neck and/or chemotherapy were investigated in 54 Hodgkin's and 72 non-Hodgkin's lymphoma patients. These patients had received radiation therapy with doses ranging from 2000 to 4000 rad (median 3600 rad) to the cervical or mantle fields and/or multiple-agent chemotherapy following usual staging procedures. Palpable abnormalities of the thyroid were found in 15 patients. The patients with irradiation to the neck had a higher incidence of hypothyroidism than those patients treated with chemotherapy alone (31/74 vs. 8/52, P less than 0.001 for TSH and 10/74 vs. 1/52, P less than 0.025 for T4). A higher frequency of elevated serum TSH levels and antithyroid antibodies were also observed in patients receiving radiation therapy alone to the neck than in those receiving both radiation therapy and chemotherapy (19/33 vs. 12/41, P less than 0.025 for TSH and 16/33 vs. 7/41, p less than 0.01 for antibodies), suggesting that chemotherapy agents may reduce the thyroid dysfunction induced by irradiation. There was no difference in prevalence of elevated TSH levels following irradiation to the neck between patients in whom lymphangiogram was or was not performed (21/51 vs. 10/23).

Thyroid-Blocking Activity of Chlorpropamide in a Diabetic Patient With Hyperthyroidism

To the Editor. —The oral hypoglycemic agents, the sulfonylurea compounds, are used by many physicians in the treatment of patients with insulinindependent diabetes mellitus. In addition to the well-known hypoglycemic actions of the sulfonylurea compounds, they also exert a less-recognized antithyroid activity similar to propylthiouracil. 1-3 This antithyroid activity of the sulfonylurea compounds is much weaker in comparison to propylthiouracil, and, in the usual therapeutic range, patients receiving sulfonylurea compounds do not manifest a hypothyroid state. 2,4 However, Hunton et al 5 have found a high incidence of hypothyroidism in their diabetic population receiving sulfonylurea compounds. Little is known about the antithyroid action of sulfonylurea compounds in diabetic patients with hyperthyroidism. Brown and Solomon 6 reported that carbutamide had no effect on thyroid function in two patients with hyperthyroidism. A patient with diabetes mellitus and hyperthyroidism had normal thyroid study results induced by chlorpropamide. Report of a Case.

Incidence of hypothyroidism after 131I therapy for hyperthyroidism. Relation to pretherapy serum levels of T3, T4 and thyroid antibodies.

A correlation is reported between serum levels of triiodothyronine (S-T3) and thyroxine (S-T4) before treatment, as well as levels of thyroid antibodies before treatment, and the development of hypothyroidism following 131I therapy in 86 patients with hyperthyroidism. Patients with marked elevation of S-T3 or S-T4 had demonstrable antibodies to thyroid cytoplasmic antigen more often than those with normal or moderately elevated levels, and patients with markedly elevated levels of S-T3 also had a higher incidence of hypothyroidism after treatment. Patients with nodular thyroid glands and with markedly elevated levels of S-T3 required a larger number of 131I doses before no signs of hyperthyroidism persisted in comparison to those with moderately elevated levels.

STANDARD DOSE 131I THERAPY FOR HYPERTHYROIDISM CAUSED BY AUTONOMOUSLY FUNCTIONING THYROID NODULES

Thirty-one patients with hyperthyroidism shown on scintigram to have autonomously functioning thyroid nodules were treated with a standard dose of 15 milliocuries (mCi) of 131I. Of thirty patients who have been followed up for a least 6 months to over 3 years, all but one patient were euthyroid after a single dose. Repeat scintigram and Thyrotropin Releasing Hormone (TRH) test after therapy confirmed that twenty-five patients were cured of the disease. Only one patient developed hypothyroidism. This simplified standard dose regimen of radioiodine is effective in the treatment of hyperthyroidism caused by autonomously functioning nodules and is not complicated by the high incidence of hypothyroidism that is observed following radioiodine therapy of Graves' disease.

Thyroid function after radiation and surgery for head and neck cancer

Preoperative radiation followed by surgical excision is accepted therapy for head and neck cancer. The effects of these modalities on thyroid function were evaluated in a prospective study. Sixty-one patients were given cobalt 60 radiation. Results showed that 41 patients (67%) were euthyroid, 12 patients (20%) were clinically and chemically hypothyroid, and 8 patients (13%) had transient loss of thyroid reserve. Permanent hypothyroidism occurred frequently in patients with hemithyroidectomy, but rarely in those treated with radiation alone. Onset of hypothyroidism was zero to six months, with transient loss of thyroid reserve occurring up to 18 months. This constitutes the initial report of an ongoing systematic study of thyroid function in such patients. The high incidence of hypothyroidism indicates a need for careful periodic evaluation.

Thyroid Function After Radiation and Surgery for Head and Neck Cancer

Preoperative radiation followed by surgical excision is accepted therapy for head and neck cancer. The effects of these modalities on thyroid function were evaluated in a prospective study. Sixty-one patients were given cobalt 60 radiation. Results showed that 41 patients (67%) were euthyroid, 12 patients (20%) were clinically and chemically hypothyroid, and 8 patients (13%) had transient loss of thyroid reserve. Permanent hypothyroidism occurred frequently in patients with hemithyroidectomy, but rarely in those treated with radiation alone. Onset of hypothyroidism was zero to six months, with transient loss of thyroid reserve occurring up to 18 months. This constitutes the initial report of an ongoing systematic study of thyroid function in such patients. The high incidence of hypothyroidism indicates a need for careful periodic evaluation.

The Treatment of Graves Disease

To the Editor.— The authors cited the paper by Nofal et al to demonstrate the high incidence of hypothyroidism following radioactive iodine therapy, but failed to mention that in the same study the rate of thyroid hypofunction ten years after subtotal thyroidectomy was 43%. Although it is generally agreed that the incidence of hypothyroidism is higher following iodine 131 therapy than after surgery, the difference is not tremendous. Furthermore, recent study by Wood, Peterson, and Ingbar concludes that progressive impairment of thyroid function is a frequent termination of the natural history of Graves disease. Thus, untreated patients, as well as those treated with radioactive iodine administration or subtotal thyroidectomy, may develop hypothyroidism that can be adequately managed with daily administration of one tablet of a thyroid preparation. Recurrence of hyperthyroidism occurs in up to 17.2% of patients with Graves disease who undergo thyroidectomy (Hershman), while 90% of patients are cured

The Treatment of Graves Disease

To the Editor.— The widespread use of radioactive iodine as a definitive treatment of Graves disease began approximately in 1950. Initial reports of excellent results with this agent and its ability to be used on outpatients casued it to be the preferred treatment, and it appeared to eliminate surgery in this disease. In the same era, the long-term use of antithyroid drugs, in an effort to obtain permanent remission, was reported and recommended. Subsequently, evaluation of these two methods of treatment has revealed serious deficiencies. Those patients treated with radioactive iodine frequently required multiple doses of the drug, resulting in prolongation of a serious illness, which was particularly disadvantageous in women in the childbearing time of their lives. It also became apparent that successful treatment with radioactive iodine was accompanied by a high incidence of hypothyroidism (45% to 70%), requiring lifetime thyroid replacement. 1 Attempts to use a lower dose

Graves' disease in the male. A review of 241 cases treated with an individually calculated dose of sodium iodide I 131.

This report encompasses a 20-year study of 241 male patients with Graves' disease. All patients received a therapeutic dose of sodium iodide I 131 calculated from the 24-hour thyroid uptake, the effective half-life of the retained 131 I tracer dose, and the gland weight. The gland weight was determined by an empirical weight formula from the thyroid scintigram. Forty-five percent of the total patient group and 74% of the Negro patients required multiple doses. Patients who required multiple doses had more severe laboratory abnormalities and lost more weight. These patients also became hypothyroid later and ultimately had a higher incidence of hypothyroidism than patients who received single doses. The mean incidence of hypothyroidism for the entire series was 27.8%. The actual number of millicuries of 131 I required to deliver the therapeutic dose had little or no relation to the ultimate therapeutic effect.

Graves' Disease in the Male

This report encompasses a 20-year study of 241 male patients with Graves' disease. All patients received a therapeutic dose of sodium iodide I 131 calculated from the 24-hour thyroid uptake, the effective half-life of the retained 131 I tracer dose, and the gland weight. The gland weight was determined by an empirical weight formula from the thyroid scintigram. Forty-five percent of the total patient group and 74% of the Negro patients required multiple doses. Patients who required multiple doses had more severe laboratory abnormalities and lost more weight. These patients also became hypothyroid later and ultimately had a higher incidence of hypothyroidism than patients who received single doses. The mean incidence of hypothyroidism for the entire series was 27.8%. The actual number of millicuries of 131 I required to deliver the therapeutic dose had little or no relation to the ultimate therapeutic effect.

Prediction of Hypothyroidism after Partial Thyroidectomy for Thyrotoxicosis

Hypothyroidism is one of the major complications after thyroidectomy for thyrotoxicosis, but the factors responsible are not well defined. In an attempt to define these factors 278 patients operated on in 1965-9 were studied in detail. The overall incidence of hypothyroidism was 49%. The high incidence of hypothyroidism during 1965-6 led to a policy of leaving larger remnants in the later years of the study, and it became apparent that the most important aetiological factor in postoperative hypothyroidism was small remnant size. There seemed to be an association between the incidence of hypothyroidism and the presence of antithyroglobulin antibodies, but this association was not statistically significant. The data suggested that blood group O might be more common and blood group A less common in hypothyroid patients. The incidence of hypothyroidism seemed to be uninfluenced by the age or sex of the patient, the size of the gland, or the amount and duration of preoperative antithyroid drug therapy.Though a reasonable prediction of the incidence of hypothyroidism can be made for a group of patients on the basis of remnant size, the fate of the individual can be predicted only within very wide limits. An indication of the future status of the individual patient at one year and subsequently does, however, seem possible from serum protein-bound iodine estimations at one and four months after operation. Hypothyroidism developing later than one year after operation has not been observed in this series. The ability to assess thyroid status early after surgery is of some merit in the long-term supervision of the postoperative thyrotoxic patient, and in this respect surgical treatment seems to have some advantage over radioiodine therapy.