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Pustulosis palmoplantaris and chronic eczematous hand dermatitis. Treatment, epidermal Langerhans cells and association with thyroid disease.

Long-standing hand and foot dermatoses, e.g. pustulosis palmoplantaris (PPP) and chronic eczematous hand dermatitis, severely affect the patients' quality of life. The cause of PPP is unknown and the disease usually responds unsatisfactorily to treatment. The aims of the studies of PPP were to determine the prevalence of thyroid disease and to evaluate the relative merits of treatment with etretinate, psoralen photochemotherapy (PUVA), and a combination of the two. Furthermore, epidermal Langerhans cells (LC) were quantified in lesional skin before and after treatment. The prevalence of thyroid disease was significantly increased in a group of PPP patients compared to normal individuals and psoriasis patients. Both hypo and hyperthyroidism were found. In addition, circulating autoantibodies to thyroid antigens were more common in patients with PPP than in the control group. The thyroid status was further examined in a new and larger group of PPP patients, including a 4-year follow-up examination of those with thyroid antibodies or subclinical thyroid dysfunction. The increased prevalence of thyroid diseases was corroborated when this PPP group was compared to an age and sex-matched control population sample from the same city. Some patients also showed biochemical evidence of gastric autoimmunity. Ninetyfour percent of the PPP patients were smokers at the time of onset of the skin disease, compared to 33% of the subjects in a control group. Patients with treatment-resistant PPP were recruited for a randomised, double-blind and placebo-controlled trial. A combination of etretinate and PUVA was more effective than monotherapy with etretinate or PUVA. The latter were equally effective. Etretinate frequently provoked side effects. Follow-up examinations showed a high relapse rate. Epidermal LC were visualised with monoclonal antibodies to Leu 6 and HLA-DR antigens utilizing an immunoperoxidase technique. Their number was increased in lesional skin. The number of HLA-DR positive LC was decreased following etretinate, and normalised with etretinate + PUVA. Chronic eczematous hand dermatitis is a common clinical challenge. These studies aimed at an evaluation of PUVA and UVB phototherapy in patients with recalcitrant lesions and to enumerate epidermal LC before and after treatment. PUVA was a highly effective mode of treatment and cleared all treated hands. UVB was better than no treatment but the dermatitis did not clear in any patient. The number of epidermal LC was increased in lesional palmar skin in both allergic contact dermatitis, irritant contact dermatitis and hyperkeratotic dermatitis of the palms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Lack of increased serum interleukin-6 and soluble IL-6 receptor concentrations in patients with thyroid diseases following recombinant human interferon alpha therapy.

BACKGROUND: Serum interleukin-6 (IL-6) concentrations are frequently elevated in inflammatory thyroid diseases, such as subacute thyroiditis and amiodarone induced thyroiditis. We and others have recently observed that recombinant interferon-alpha (rIFN-alpha) therapy for chronic, active viral hepatitis and malignant disorders may induce thyroid dysfunction, including thyrotoxicosis secondary to thyroiditis. Serum IL-6 and its soluble receptor (sIL-6R) have been measured for the first time in patients with chronic active hepatitis receiving rIFN-alpha therapy. METHODS: Studies were carried out in 37 patients treated with rIFN-alpha for chronic, active viral hepatitis. Thyroid function tests and serum IL-6 and sIL-6R were measured before and during rIFN-alpha therapy. RESULTS: Six patients developed inflammatory or destructive thyrotoxicosis confirmed by elevated serum free T4 or free T3 concentrations, suppressed serum thyroid-stimulating hormone (TSH) values, and a low thyroid radioactive iodine uptake. Serum IL-6 and sIL-6R concentrations were not elevated in these patients with rIFN-alpha-induced thyroiditis. CONCLUSIONS: These results suggest that serum IL-6 concentrations are not useful in differentiating between inflammatory thyrotoxicosis and hyperthyroidism induced by rIFN-alpha therapy as is the case in amiodarone-induced thyrotoxicosis. It is possible that rIFN-alpha therapy could be associated with an inhibitory effect of rIFN-alpha on the release of IL-6 from damaged thyroid cells and not on the basal secretion of IL-6.

Antigens, CD↗

Thyroid function after mantle irradiation in Hodgkin's disease.

We studied the thyroid function of 64 patients with Hodgkin's disease who received mantle irradiation during the period 1966 to 1976. More than two thirds (44 of 64) had some thyroid dysfunction. Twenty had mild dysfunction manifested by an abnormal thyroid-stimulating hormone response to thyrotropin-releasing hormone. Twenty had what could be termed compensated hypothyroidism while four were overtly hypothyroid. The severity of dysfunction was not related to age, sex, or chemotherapy. We found, however, that decreased thyroid function was inversely proportional to the length of time between a diagnostic lymphangiogram and the radiation therapy. These results are consistent with the hypothesis that the iodine load of the lymphangiogram renders the thyroid gland more radiosensitive. Thyroxine suppression of the thyroid gland during the period from the lymphangiogram through the termination of radiation therapy is suggested as a means of avoiding thyroid injury.

Ethiodized Oil↗

Is hepatitis C virus a risk factor for thyroid autoimmunity?

The role of hepatitis C virus (HCV) in inducing thyroid autoimmunity is still under discussion and to assess the prevalence of thyroid autoantibodies and thyroid disease in the general population and to analyse the role of HCV in inducing thyroid autoimmunity. We studied 697 subjects residing in Arsita (a small town in central Italy). Thyroid autoantibodies and nonorgan-specific autoantibodies (NOSAs) were tested in each subject, who were also screened for anti-HCV antibodies; all subjects found positive to HCV-RNA were considered as being HCV-infected. Thyroid function tests were performed in all subjects positive for thyroid autoantibody. Seventy-one subjects were found HCV-positive; four of these (5.6%) were positive for at least one thyroid autoantibody, as opposed to 7 (4.9%) of the 142 sex- and age-matched controls of the same population (P = n.s.). Thyroid dysfunction was found in 2/4 HCV-positive, and in 1/7 HCV-negative subjects with thyroid autoantibodies (P = n.s.). NOSAs were significantly more common in HCV-positive than in HCV-negative subjects (P < 0.0001). Hence HCV per se is not responsible for thyroid autoimmune dysfunction, whereas HCV does seem to induce NOSAs. It should be taken into account, however, that the phenotypic expression of autoimmune diseases is obviously influenced by a number of risk factors, including genetic predisposition, female sex and infectious agents, that could trigger the onset of the disease.

Adult↗

Auditory brain-stem evoked potentials in patients with thyroid and parathyroid dysfunction: adaptation to chronic hormonal dysequilibrium.

Auditory Brainstem Evoked Potentials (ABEPs) and pure tone audiograms were obtained from 24 patients with parathyroid dysfunction (17 hypercalcemia and 7 hypocalcemia) and 12 patients with thyroid dysfunction (6 hyperthyroid and 6 hypothyroid) and from 10 control subjects. ABEPs were characterized by I-V interpeak latency difference at 10/sec click rate and by the effect of increasing stimulus rate to 55/sec. None of the ABEP measures were significantly affected by levels of serum calcium, thyroid hormones or their interactions. Moreover no correlation was found between biochemical and electrophysiological measures. This stability of ABEP measures contrasts with earlier reports on acute effects of calcium and thyroid hormonal levels on auditory brainstem evoked potentials. We propose that chronic calcium or thyroid hormonal homeostatic changes are associated with adaptive mechanisms resulting in normal function of the auditory brainstem.

Adaptation, Biological↗

Thyroid storm presenting as multiple organ dysfunction syndrome.

Thyroid storm is a rare disorder characterized by hypertension, hyperthermia, and multiple systems involvement. Early recognition and treatment of thyroid storm are essential in reducing morbidity and mortality from this disorder. We present the case of a patient with an atypical (normothermic, normotensive) presentation of thyroid storm, accompanied by multiple organ dysfunction syndrome, including lactic acidosis and liver dysfunction, both of which are very rare complications. This case highlights both the multiple organ systems that can be involved in thyroid storm and the importance of recognizing atypical presentations of thyroid storm.

Adult↗

Treatment of subclinical hypothyroidism reverses ischemia and prevents myocyte loss and progressive LV dysfunction in hamsters with dilated cardiomyopathy.

Growing evidence suggests that thyroid dysfunction may contribute to progression of cardiac disease to heart failure. We investigated the effects of a therapeutic dose of thyroid hormones (TH) on cardiomyopathic (CM) hamsters from 4 to 6 mo of age. CM hamsters had subclinical hypothyroidism (normal thyroxine, elevated TSH). Left ventricular (LV) function was determined by echocardiography and hemodynamics. Whole tissue pathology and isolated myocyte size and number were assessed. TH treatment prevented the decline in heart rate and rate of LV pressure increase and improved LV ejection fraction. The percentage of fibrosis/necrosis in untreated 4-mo-old CM (4CM; 15.5 +/- 2.2%) and 6-mo-old CM (6CM; 21.5 +/- 2.4%) hamsters was pronounced and was reversed in treated CM (TCM; 11.9 +/- 0.9%) hamsters. Total ventricular myocyte number was the same between 4- and 6-mo-old controls but was reduced by 30% in 4CM and 43% in 6CM hamsters. TH treatment completely prevented further loss of myocytes in TCM hamsters. Compared with age-matched controls, resting and maximum coronary blood flow was impaired in 4CM and 6CM hamsters. Blood flow was completely normalized by TH treatment. We conclude that TH treatment of CM hamsters with subclinical hypothyroidism normalized impaired coronary blood flow, which prevented the decline in LV function and loss of myocytes.

Animals↗

Pericardial effusion as a sign of acquired hypothyroidism in children with Down syndrome.

In three children with Down syndrome and acquired hypothyroidism echocardiography was performed before and after the start of L-thyroxine treatment. Initial studies revealed pericardial effusions which resolved during treatment suggesting that they were caused by hypothyroidism. The incidence of hypothyroidism in Down syndrome is high, but the diagnosis is often missed for lack of specific clinical criteria. The finding of pericardial effusion by echocardiography may be essential in discovering thyroid dysfunction. The cases illustrate that regular thyroid function tests are important in Down syndrome.

Child↗

Postpartum thyroiditis.

The special characteristics of postpartum thyroid syndromes are summarized in Table 8. Many of the cases will pass unnoticed, although a higher detection rate is to be expected if postpartum thyroid disease becomes better known among physicians and the general public. Screening in early pregnancy of women with a previous or family history of thyroid disease and in women with other autoimmune disorders (such as diabetes mellitus type 1) may be worthwhile. The initial manifestation of postpartum thyroiditis, often appearing during the first three months postpartum, is a thyrotoxic phase characterized by a low RAIU ('painless thyroiditis' or 'destruction-induced thyrotoxicosis'). Subsequently, a transient hypothyroid phase supervenes. In a small proportion of women hypothyroidism becomes permanent. After a subsequent pregnancy recurrence is the rule. Women who are genetically disposed to Graves' disease may experience thyrotoxicosis with a high RAIU usually appearing later than three months postpartum. As the thyroid function abnormalities are usually mild and transient it is often appropriate to withhold treatment. However, in women with pronounced symptoms treatment should be started. When the postpartum period has passed gradual withdrawal of treatment should be attempted. In women who have experienced postpartum thyroid dysfunction, the risk of developing permanent thyroid disease in later life seems important and therefore long-term follow-up is recommended.

Female↗

Decreased thyroid peroxidase expression in cultured thyrocytes after external gamma irradiation.

Impairment of thyroid function has been described in up to 50% of the patients after external irradiation of the neck region as well as after mantle irradiation. In order to assess radiation-induced alterations in cultured thyroid cells, the occurrence of apoptosis and necrosis as well as the expression of thyroid peroxidase (TPO) and of two members of the 70 kD heat shock family, HSP-73 and HSP-72, were analysed following gamma irradiation. Human thyroid epithelial cells (TEC) were purified from surgical tissue specimens, were cultured and irradiated with a single dose of 5 Gy or 50 Gy using Co60 as radioactive source. Analysis was performed 1, 3 and 5 day(s) after irradiation. Apoptosis and necrosis were assessed by DNA staining with propidium iodide and FACS analysis. TPO and HSP expression by SDS-PAGE and Western blotting. The cell viability of TEC was not affected by irradiation and there was no induction of HSP-72, a sensitive indicator of acute cellular stress. Interestingly, the expression of TPO, a key enzyme of thyroid hormone synthesis, decreased significantly in irradiated TEC, while HSP-73 expression remained unchanged. Decreased expression of TPO with a resulting suppression of thyroid hormone synthesis could contribute to an early development of thyroid dysfunction following irradiation. Thus, analysis of thyroid function, even early after external radiation therapy of the neck or after total body irradiation, seems to be indicated.

Apoptosis↗

Biologic variation is important for interpretation of thyroid function tests.

Large variations exist in thyrotropin (TSH) and thyroid hormones in serum. The components of variation include preanalytical, analytical, and biologic variation. This is divided into between- and within-individual variation. The latter consists of circadian and seasonal differences although there are indicators of a genetically determined starting point. The ratio of within- to between-individual variation describes the reliability of population-based reference ranges. This ratio is low for serum TSH, thyroxine (T(4)) and triiodothyronine (T(3)) indicating that laboratory reference ranges are relatively insensitive to aberrations from normality in the individual. Solutions are considered but reducing the analytical variation below the calculated analytical goals of 7%, 5% and 12% for serum T(3), T(4), and TSH does not improve diagnostic performance. Neither does determination of the individual set-point and reference range. In practice this means that population-based reference ranges are necessary but that it is important to recognize their limitations for use in individuals. Serum TSH responds with amplification to minor alterations in T(4) and T(3). A consistently abnormal TSH probably indicates that T(4) and T(3) are not normal for the individual even when inside the laboratory reference range. This underlines the importance of TSH in diagnosis and monitoring of thyroid dysfunctions. Also, it implies that subclinical thyroid disease may be defined in purely biochemical terms. Under critical circumstances such as pregnancy where normal thyroid function is of importance for fetal brain development, subclinical thyroid disease should be treated. Even TSH within the reference range may be associated with slightly abnormal thyroid function of the individual. The clinical importance of such small abnormalities in thyroid function in small children and pregnant women for brain development remains to be elucidated.

Circadian Rhythm↗

Amyloid goiter. A clinicopathologic study of 14 cases and review of the literature.

The authors report the clinicopathologic features of 14 cases of amyloid goiter (AG). Eleven patients were males and three females with ages ranging from 23 to 75 years (median, 54 years). Eight patients had secondary amyloidosis and six had primary amyloidosis. Nine cases were identified at autopsy. In symptomatic patients (n = 5), the clinical presentation included a nontender, rapidly enlarging neck mass with associated dysphagia, dyspnea or hoarseness. Clinical or laboratory evaluation failed to detect evidence of thyroid dysfunction. The histologic appearance of the thyroid predominantly consisted of diffuse amyloid deposition surrounding thyroid follicles. In two cases, a nodular pattern of amyloid deposition was seen resulting in compression and distortion of the follicular architecture. Areas of mature adipose tissue and focal lymphocytic thyroiditis with or without foreign-body type-giant cells were seen in approximately one third of the cases. Confirmation of amyloid was made by the presence of congophilia and apple-green birefringence under polarized-light microscopy. Immunohistochemical evaluation demonstrated the presence of amyloid A immunoreactivity. No Immunoreactivity was seen with calcitonin or thyroglobulin. Fine-needle aspiration may facilitate the diagnosis, as occurred in one the patients. In symptomatic patients, thyroidectomy is warranted to alleviate pressure symptoms.

Adult↗

A case of glomerular lipidosis accompanied by familial combined hyperlipidemia and panhypopituitarism.

This is a report of a case of glomerular lipidosis with familial combined hyperlipidemia and panhypopituitarism. A 60-yr-old woman was admitted for evaluation of hyponatremia. Administration of hydrocortisone normalized the level of serum Na. A pituitary hormone-stimulating test and brain computed tomography revealed panhypopituitarism with an empty sella. Glucocorticoid deficiency due to secondary hypoaldosteronism was thought to have caused the Na loss. She had been treated for thyroid dysfunction and hyperlipidemia with replacement of thyroid hormone and a lipid-lowering drug. Hyperlipidemia changed from type V into IIa in 4 yr. Furthermore, one of her brothers and one of her sons were suspected to have type IV hyperlipidemia. Familial combined hyperlipidemia accompanied by secondary hypothyroidism was thought to have increased the levels of both total cholesterol and triglyceride. Two renal biopsies in 3 yr showed lipid deposits in the mesangial cells and indicated a positive correlation between the levels of serum lipids and lipid deposits in glomeruli, which suggested an important role of abnormal lipid metabolism in the progression of glomerular lipidosis.

Empty Sella Syndrome↗

Value of thyroid follow-up registers.

In this study from a county in southern Sweden 269 of 271 patients (99.3%) treated with radioiodine for hyperthyroidism over a two-year period were followed up five years later. The routine procedures at hospital clinics and primary health care centres were studied. A high number of toxic multinodular goitre (n = 113; 42.0%) and toxic adenoma (n = 76; 28.3%) emerged, 80 patients (29.7%) had toxic diffuse goitre (Graves's disease). During the five-year follow-up the cumulative incidence of hypothyroidism in the various goitre groups was 10.7%, 23.9%, and 57.5% respectively. Altogether 76 patients (28.3%) were diagnosed hypothyroid. Nine patients were lost to regular follow-up; elevated TSH and low or normal T4-concentrations were found in two of them. We propose a register system to enable detection of thyroid dysfunction after radioiodine treatment and other thyroid patients in primary health care.

Adult↗

Prevalence of thyroid autoimmunity in insulin dependent diabetes mellitus in the Bayamon region.

The purpose of this study was to describe our experience in the Bayamon region with respect to the prevalence of thyroid autoimmunity in our pediatric diabetic population. We identified a total of 78 patients with IDDM and all were examined to ascertain the presence of goiter. Thyroid profile, free thyroxine, thyrotropin, and thyroid microsomal autoantibodies were measured by radioimmunoassay in 65 of these patients. The data was analyzed using the Chi square test in order to correlate thyroid dysfunction with respect to sex and thyroid autoimmunity. Our results revealed a prevalence of thyroid autoimmunity in our IDDM patients of 15%, 40% of them had a goiter (p less than 001) and most of them were female (9 of 12). This is the lowest prevalence of thyroid autoimmunity in diabetic children reported in Hispanic groups in the United States thus far.

Adolescent↗

Thyroid hormones and autoantibodies in pregnant patients with thyroid diseases.

Serum concentrations of thyroid stimulating hormone (TSH) and thyroid autoantibodies in pregnant patients with thyroid disease at various stages of pregnancy were determined by in-house ELISAs. In normal pregnancy, serum TSH levels were significantly elevated (p < 0.05) from 13 weeks of gestation. The normal reference ranges for TSH for the second (0.6-5.0 mIU/l) and third trimester (0.6-5.6 mIU/l) were significantly higher (p < 0.05; p < 0.01 respectively) compared to 0.4-4.5 mIU/l for the first trimester. In pregnant thyroid patients, serum TSH levels correlated highly (p < 0.001) to T4 (r = 0.740), FT4I (r = 0.683) and MicAb (microsomal antibodies) (r = 0.825) but weaker (p < 0.01) to T3 (r = -0.512), FT3I (r = 0.520) and TgAb (thyroglobulin antibodies) (r = 0.618). Thus, measurement of TSH with the highly sensitive ELISA (enzyme linked immunosorbent assay) would form a useful first line test for thyroid dysfunction in pregnancy while measurement of thyroid autoantibodies would aid in the diagnosis of autoimmune hypothyroidism.

Adult↗

Relation of thyroid disfunction, thyroid autoantibodies, and renal function.

Fifty-eight patients with thyroid dysfunction were included, comparing 27 healthy subjects to evaluate the relationship between thyroid autoimmunity, thyroid functional status, and renal function. Regardless of clinical status, hypothyroidism was defined as T3-T4 upper limit of normal, and hyperthyroidism was defined as T3-T4>normal limits and TSH <0.1 mcU/mL. In all participants, serum antithyroperoxidase level, serum antithyroglobulin level, creatinine clearance (CC), and urinary albumin excretion rate (UAER) in 24-h urine collections were measured. Of 85 persons, 41 patients ages 20 to 71 years (median; 44) had hypothyroidism, 17 patients ages 22 to 56 years (median; 32) had hyperthyroidism, and 27 subjects ages 20 to 67 years (median; 50) were normal. Regarding thyroid autoantibody positiveness, the positive group had a higher UAER than the negative group (30.2 mg/day, 20.8 mg/day, respectively; p=0.05). In hypothyroid patients, UAER was significantly higher than in hyperthyroid patients and control subjects (30.1 mg/day, 11.8 mg/day, 10.5 mg/day, respectively; p<0.001). In the hypothyroid population, with regard to UAER and CC, we could not find a significant difference between the thyroid autoantibody positive and negative groups. In view of CC, hypothyroid patients had significantly lower CC than the hyperthyroid group (79.0 mL/ min, 86.5 mL/min, respectively; p<0.01). A careful control of the renal function in thyroid diseases should be evaluated. Renal dysfunction seems to be secondary to hypothyroidism rather than thyroid autoimmunity.

Adult↗

Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout.

BACKGROUND: The long-term effects of ionising radiation, including radioiodine, on thyroid function are not well known. We compared thyroid immunity and function in two groups of children from Belarus, one of whom was exposed to the radioactive fallout of Chernobyl. METHODS: We measured serum free thyroxine 4 (free T4), free T3, and thyrotropin hormone (TSH) and the prevalence of thyroid autoantibodies (antithyroglobulin and antithyroperoxidase), in 287 children or adolescents living in Hoiniki (average caesium contamination of 5.4 Ci/km2). We also studied 208 children and adolescents living in Braslav (average contamination <0.1 Ci/km2), who were age 12 years or less at the time of the Chernobyl accident. FINDINGS: The prevalence of antithyroglobulin or antithyroperoxidase, or both, was significantly higher (p=0.0001) in individuals living in Hoiniki (56 [19.5%] of 287) than in those living in Braslav (eight [3.8%] of 208). In both villages, no sex differences were found in the antibody prevalence before age 13 years. Thereafter, a significantly higher prevalence of thyroid autoantibodies was found in girls from Hoiniki. The increase in the prevalence of circulating antibodies in the contaminated group was already apparent in individuals who, at the time of the accident, were in utero or newborn (15.7%), and was even more pronounced in children of 9 years or more (35.1%). No major alterations of serum FT-4, FT-3, or TSH were found. INTERPRETATION: 6-8 years after the Chernobyl accident, a significant increase in thyroid autoimmunity was found in children exposed to radioactive fallout. Pubertal age in girls is a risk factor for increased prevalence of thyroid autoimmunity. The autoimmune phenomena are limited to an increased prevalence of circulating thyroid autoantibodies without evidence of significant thyroid dysfunction. The future development of clinically relevant thyroid autoimmune diseases, especially hypothyroidism, is a possibility.

Adolescent↗