Bioelectrical impedance assessment of body composition in thyroid disease.

To assess the metabolic effects of thyroid disease, body composition was determined by bioimpedance analysis (BIA) in 72 patients with untreated hyperthyroidism (mean age 48.7 +/- 1.9 years) and 26 patients with untreated hypothyroidism (63.8 +/- 3.4 years). Bioelectrical whole body resistance (R) and reactance (Xc) were used for computerized calculation of lean body mass (LBM), body cell mass (BCM), extracellular mass (ECM) and body fat (BF). Compared with age- and sex-matched healthy controls the most sensitive parameter indicating excess thyroid hormone was the ECM/BCM ratio which was markedly elevated in all hyperthyroid subjects. ECM/BCM alteration resulted from marked depletion of BCM with concomitant expansion of ECM. BCM change is thought to be predominantly due to a loss of muscle mass while ECM rise may reflect an increase in extracellular fluids. In contrast, hypothyroidism was characterized by an increase in BF besides a relatively unaffected LBM component. Serum parameters of thyroid function (tri-iodothyronine (T3), free thyroxine, TSH) did not correlate with the determinants of body composition except for a slight inverse relationship between the phase angle (Xc/Rx180 degrees/pi) and T3 concentration in Graves' disease patients. We conclude that hyperthyroidism is primarily accompanied by quantitative as well as qualitative changes in the lean body while considerable fat increase is the most important feature of hypothyroidism. Severity of body composition derangement cannot be predicted from the degree of thyroid dysfunction. BIA could become a useful tool which allows objective determination of even subtle metabolic manifestations of thyroid disease and should, therefore, complement conventional clinical and biochemical assessment.

[Assessment of the hypothalamic-hypophyseal-adrenal axis in patients with chronic obstructive lung disease. Comparison of inhalant with systemic glucocorticoid therapy]. / Evaluation der hypothalamo-hypophysär-adrenalen Hormon-Achse bei Patienten mit chronisch-obstruktiver Atemwegserkrankung. Vergleich einer inhalativen mit einer systemischen Glucocorticoidtherapie.

OBJECTIVE: The action of inhalation and systemic treatment of chronic obstructive pulmonary disease by suppressing the hypothalamo-hypophyseal-adrenal axis was compared in patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Adrenocorticotropic hormone (ACTH) and cortisol concentrations were evaluated after a corticotropin-releasing-hormone (CRH)-test in 50 patients (aged 43 +/- 14 years) with chronic obstructive pulmonary disease (COPD) receiving inhalant glucocorticoid treatment (IGC), 61 patients (aged 54 +/- 11 years) with COPD on systemic glucocorticoid treatment (SGC) and 50 healthy volunteers (32 +/- 4 years). RESULTS: All 50 patients on IGC had normal CRH test results. 30 of 61 patients with SGC had decreased cortisol response (12 patients had no and 18 a reduced rise in cortisol). ACTH concentration was lower in patients on IGC than in the control group (basal ACTH 15.6 pg/ml and 24.5 pg/ml, respectively; after stimulation 40.3 vs 54.4 pg/ml, respectively). But systemic glucocorticoid treatment clearly caused suppression of basal (12.1 pg/ml) and stimulated (27.4 pg/ml) ACTH levels with correspondingly decreased cortisol levels (basal: 75.1 and 118.7 ng/ml [IGC], respectively, and after stimulation 128.5 and 225.9 ng/ml). CONCLUSIONS: Patients with COPD on inhalant glucocorticoid treatment have a clearly lower risk of adrenal cortical insufficiency than those on oral glucocorticoid treatment. But some suppression of ACTH secretion is demonstrable even in the former. Clinical significance of these findings seems unlikely. Development of adrenal cortical insufficiency need not be feared in patients treated with inhalant glucocorticoids.

Iodide or L-thyroxine to prevent recurrent goiter in an iodine-deficient area: prospective sonographic study.

In a randomized study, prevention of goiter recurrence with L-thyroxine was compared with pure iodide substitution after thyroid surgery for nodular goiter in an iodine-deficient area. Altogether 107 patients were followed up for 52 weeks after thyroid resection. The thyroid volume was determined sonographically. Free thyroxine, total thyroxine, thyrotropin, thyroglobulin, and antibodies to thyroglobulin and thyroid peroxidase were measured. The thyroid volume decreased slightly over the course of a year in the two therapy groups. There was no significant difference between the two groups. Recurrences were seen with both L-thyroxine medication and iodide substitution. The thyroglobulin levels fell significantly over the 52-week follow-up period in the iodide group. Antibody formation was not observed under iodine substitution. In an area of iodine deficiency, substitution with iodide is just as effective as medicating the patients with L-thyroxine for preventing recurrences.

[Therapy of endemic goiter with iodide or l-thyroxine in older patients]. / Therapie der endemischen Struma mit Jodid oder L-Thyroxin bei älteren Patienten.

OBJECTIVE: To compare the efficacy of iodide (300 micrograms daily) with that of levothyroxine (1.5 micrograms/kg daily) in the treatment of endemic goitre in middle-aged and elderly persons. The possible occurrence of antibodies against thyroid peroxidase and thyroglobulin was also tested. PATIENTS AND METHODS: 67 patients (54 women, 13 men; aged over 40 years, average 53.5 years) with endemic goitre, excluding toxic goitre, were randomly treated with either iodine or thyroxine. Every 3 months for one year their thyroid volume was obtained by ultrasound and the activities of thyroid hormone (TH) and thyroid stimulating hormone (TSH) and the concentration of antibodies against peroxidase and thyroglobulin were measured. RESULTS: In patients on levothyroxine the thyroid volume had already markedly decreased after 3 months (P < 0.0001), diminishing by 15.4% at 12 months. Volume reduction in the group on iodine was 16.2% at one year. There was no significant difference between the two medications and no case of antibody production in the iodine group. CONCLUSIONS: Treatment of endemic goitre with iodine alone is efficacious even in middle-aged or elderly patients, toxic goitre having been excluded. There was no evidence of antibody production against thyroid antigens at the stated iodine dosage.

High-dose intravenous therapy with 7S immunoglobulins in autoimmune endocrine ophthalmopathy.

OBJECTIVE: Endocrine ophthalmopathy is an autoimmune disorder of the retroorbital space tissues which is generally associated with thyroidal Graves' disease. Its pathogenetical aspects, clinical appearance and diagnostic procedures are reviewed. Therapeutic options include both established and more experimental approaches. Increasing use of intravenously administered immunoglobulin preparations has been noted in a variety of autoimmunologically mediated diseases. We report preliminary data of an observational trial on high-dose immunoglobulin treatment including 10 patients suffering from thyroid eye disease. METHODS: Ophthalmopathy which had not been present for longer than 12 month and Graves' disease with an euthyroid metabolic state at the time of the investigation were the inclusion criteria. Therapy was commenced with a high initial immunoglobulin dose of 20 g/d over a period of five days, and 4 further doses of 20 g each were administered at intervals of 4 weeks. RESULTS: No significant decrease was found in the clinical ophthalmopathy index and in thyroid-specific autoantibody levels. The eye muscle index, determined radiologically by orbital computed tomography as a parameter for inflammatory eye muscle involvement, also did not change significantly during therapy. CONCLUSION: In contradiction to previous reports, our results do not at present allow a general recommendation of high-dose immunoglobulin treatment in thyroid-related ophthalmopathy. Immunoglobulin therapy might be effective in selected patients, but criteria for selection have to be defined.

[Subclinical hypercortisolism in incidentally detected adrenal adenoma]. / Subklinischer Hypercortisolismus bei zufällig entdeckten Nebennierentumoren.

AIM OF STUDY: To define in a prospective study the prevalence and manifestations of subclinical hypercortisolism in a sizeable group of patients with incidentally detected adrenal adenoma. Such tumour - although usually clinically silent - may cause discrete endocrine dysfunctions. PATIENTS AND METHODS: Between 1990 and 1994, 85 consecutive patients with incidentally discovered adrenal adenoma were investigated (54 women, 31 men; mean age 54.1 +/- 13 [24-81] years). In addition to history and clinical examination all patients had a low-dose dexamethasone suppression test (2mg) and their morning basal plasma ACTH concentration was measured. The diagnosis of subclinical hypercortisolism was made if there was inadequate suppression of cortisol after dexamethasone administration, plasma ACTH level was decreased and there were no clinical signs of Cushing's syndrome. RESULTS: Five of the patients fulfilled the criteria of subclinical hypercortisolism (prevalence of 6%). One of them had oligomenorrhoea, another arterial hypertension, and three had mild histological proof of adrenal adenoma. Postoperatively the patient with oligomenorrhoea had normal menstrual cycles, while in all others with subclinical hypercortisolism excision of the tumour had no influence of their clinical state. CONCLUSIONS: Subclinical hypercortisolism is rare, but is one of the most common endocrine disorders in patients with incidental adrenal adenoma. It can be diagnosed only by hormonal analysis. Once the latent cortisol excess has been eliminated, those symptoms which are due to hormonal abnormality may regress, but nonspecific signs, such as obesity or hypertension, may not necessarily improve.

Serum sex hormone-binding globulin and osteocalcin in systemic nonthyroidal illness associated with low thyroid hormone concentrations.

To test the hypothesis that patients with systemic nonthyroidal illness (NTI) and impaired thyroid hormone metabolism most commonly present with the low T3 or low T4 syndrome are in an euthyroid status at the tissue level, we determined serum sex hormone-binding globulin (SHBG) and osteocalcin (OC) as parameters for thyroid hormone availability to liver and bone. Serum SHBG and OC concentrations were measured in 61 severely ill patients with decreased serum levels of either T3 alone (n = 47) or both T3 and free T4 (n = 14). None of the patients had primary thyroid disorder indicated by regular thyroid sonomorphology and normal basal TSH concentrations. Data were compared with values obtained from age- and sex-matched controls without impairment of thyroid hormone physiology. The respective results from the study groups and from control subjects were as follows: low T3 SHBG, 49 +/- 30 nmol/L; low T4 SHBG, 35 +/- 14 nmol/L; control SHBG, 45 +/- 28 nmol/L; low T3 OC, 0.87 +/- 0.75 nmol/L; low T4 OC, 0.75 +/- 0.71 nmol/L; control OC, 0.98 +/- 0.87 nmol/L. SHBG and OC do not differ significantly between NTI patients with low T3 or low T4 syndrome and controls, and no significant relationship was found between thyroid hormone parameters and SHBG or OC, respectively. We conclude that the term euthyroid sick syndrome applied for the condition of systemic NTI associated with reduced circulating thyroid hormone concentrations appears to be appropriate at the level of hepatocytes and osteoblasts. Data are in partial contradiction to the results of previous studies using alternative serum parameters for assessment of peripheral thyroid hormone action (e.g. angiotensin-converting enzyme). Due to the tissue specificity of the biochemical serum markers, conflicting results may be explained by organ-specific differences in local thyroid hormone exposure. In case of doubt, SHBG and OC determinations may help specify peripheral thyrometabolic status in NTI.

Chronic intestinal giardiasis with isolated levothyroxine malabsorption as reason for severe hypothyroidism--implications for localization of thyroid hormone absorption in the gut.

We report a case of isolated levothyroxine malabsorption in the course of chronic intestinal giardiasis, leading to severe hypothyroidism. Infection with Giardia lamblia was proved histologically by jejunal biopsy. Treatment with metronidazole resulted in complete elimination of parasites and recovery of regular intestinal thyroid hormone absorption. Stable euthyroidism was accomplished with common replacement doses of orally administered levothyroxine.

Augmented 17 alpha-hydroxyprogesterone response to ACTH stimulation as evidence of decreased 21-hydroxylase activity in patients with incidentally discovered adrenal tumours ('incidentalomas').

OBJECTIVE: Recent studies have indicated that the syndrome of congenital adrenal hyperplasia due to 21-hydroxylase deficiency is closely associated with the development of benign adrenocortical tumours. Tumour formation is thought to be a consequence of ACTH hypersecretion which results from the lack of glucocorticoid synthesis. The aim of this study was to evaluate 21-hydroxylase activity in patients with an incidentally discovered adrenal mass ('incidentaloma') without a history of congenital adrenal hyperplasia. DESIGN: A prospective study of 52 patients admitted to a single hospital. PATIENTS: Fifty-two consecutive subjects (mean age 56.0 years, range 24-81 years) with an incidentally discovered adrenal tumour were studied. MEASUREMENTS: The 21-hydroxylase reserve was assessed by intravenous bolus administration of 1-24 ACTH (tetracosactrin) with measurement of basal and stimulated serum 17 alpha-hydroxyprogesterone (17-OHP) concentrations. Impaired 21-hydroxylase activity was defined as an exaggerated 17-OHP response, with a 17-OHP increment exceeding 7.9 nmol/l. Basal and stimulated cortisol concentrations, and basal ACTH were also measured. RESULTS: Baseline levels of 17-OHP were normal in 44 and elevated in 8 subjects. In 37 patients (71.2%), the 17-OHP increment following ACTH administration exceeded 7.9 nmol/l, demonstrating mildly decreased 21-hydroxylase activity. In these subjects, the peak serum 17-OHP correlated with the tumour diameter. In the patients with apparently normal 21-hydroxylase activity, no significant correlation was found between 17-OHP concentrations and tumour size. All patients had a stimulated serum cortisol above 550 nmol/l reflecting intact adrenal glucocorticoid reserve. There were no other differences between the group with exaggerated and the group with normal 17-OHP increment. The tumours were removed from two women with augmented 17-OHP responses and this was followed by normalization of 17-OHP dynamics. CONCLUSIONS: Biochemical evidence for partial 21-hydroxylase defiency is a common finding in patients with an adrenal incidentaloma, even in the absence of a congenital adrenal hyperplasia history. Exaggerated 17-OHP increment is not accompanied by decreased adrenal glucocorticoid reserve. Normalization of the 17-OHP response after surgical treatment suggests that the phenomenon results from reduced 21-hydroxylase activity in the tumour, which retains ACTH responsiveness.

Effects of glucocorticoids in rheumatoid arthritis. Diminished glucocorticoid receptors do not result in glucocorticoid resistance.

OBJECTIVE: Lymphocytes of patients with rheumatoid arthritis (RA) have diminished receptor density; thus, patients with RA should show partial resistance to glucocorticoids. We investigated the glucocorticoid sensitivity of lymphocytes in RA patients compared with healthy subjects. METHODS: We determined the effects of glucocorticoids on lymphocyte proliferation and cytokine release. RESULTS: Proliferation and cytokine release were inhibited in RA patients to the same extent as in healthy controls. CONCLUSION: Diminished receptor density in RA patients does not result in glucocorticoid resistance.

Sympathetic neural blockade by thoracic epidural anesthesia suppresses renin release in response to arterial hypotension.

BACKGROUND: The renin-angiotensin and vasopressin systems, in addition to the sympathetic system, are important backup mechanisms for maintaining arterial blood pressure during circulatory challenges. We tested the hypothesis that preganglionic sympathetic blockade by thoracic epidural anesthesia interferes with the functional integrity of the renin-angiotensin system. METHODS: Renin concentrations were assessed in awake non-sedated patients in response to induced arterial hypotension both before and during sympathetic blockade by thoracic epidural anesthesia (n = 10). Heart rate (electrocardiogram) and mean arterial blood pressure (electromanometry) were recorded continuously. Active renin (radioimmunoassay), vasopressin (radioimmunoassay), and osmolality (osmometry) in arterial blood were measured intermittently: (1) at baseline, (2) during a hypotensive challenge (15 min) induced by sodium nitroprusside (titrated to decrease mean arterial blood pressure by at least 25%) with the sympathetic system intact, (3) during recovery, (4) with epidural anesthesia alone (sensory blockade T1-T11), and (5) during a second hypotensive challenge and sympathetic blockade with sodium nitroprusside titrated to the same mean arterial blood pressure as with the sympathetic system intact. RESULTS: With the sympathetic system intact hypotension almost doubled renin concentration (34 +/- 32 SD to 60 +/- 58 pg.ml-1, P = 0.019), while vasopressin concentration remained unchanged. In contrast, during sympathetic blockade and despite identical hypotension (mean arterial blood pressure 68 +/- 8 vs. 67 +/- 5 mmHg), renin concentration did not change (35 +/- 27 vs. 35 +/- 29 pg.ml-1, P = 0.5), whereas vasopressin concentration increased (4.6 +/- 2.5 to 13.4 +/- 9.4 pg.ml-1, P = 0.01). Osmolality remained unchanged. CONCLUSION: Our results indicate a key role of renal sympathetic fibers in mediating renin release during hypotension in humans, and that epidural anesthesia interferes with the functional integrity of the renin-angiotensin system.

Complete remission of metastasized adrenocortical carcinoma under o,p'-DDD.

The case of a 53 year old female patient with metastasized androgen producing adrenocortical carcinoma is presented. After initial adrenalectomy a local relapse had been treated by surgery and external irradiation. Solitary liver metastases had been resected repeatedly. Subsequently multiple liver metastases required systemic chemotherapy. Treatment with o,p'-DDD (initially 12 g/d, long term treatment 1.5-3 g/d) has resulted in a complete remission for nearly 4 years. Gastrointestinal side effects occurred initially but subsided with dose reduction of o,p'-DDD.

[Experience with presymptomatic screening of patients with C cell carcinoma of the thyroid gland]. / Erfahrungen mit präsymptomatischem Screening bei Patienten mit C-Zell-Carcinom der Schilddrüse.

Presymptomatic screening of medullary thyroid carcinoma in MEN 2A families enables the early diagnosis of this tumor burdened by significant morbidity. Biochemical screening consists of basal and stimulated serum calcitonin evaluation. Genetic screening is based on DNA analysis using linked DNA markers. Thyroidectomy at an occult tumor stage may provide curative treatment. Calcitonin measurement was carried out in 58 apparently unaffected family members at risk of 11 MEN 2A patients. In 9 individuals calcitonin elevation was detected. All 9 underwent thyroidectomy. Histological examination confirmed medullary thyroid carcinoma in 8 patients and in 1 case C-cell-hyperplasia. Postoperatively 8 patients (89%) are clinically and biochemically tumor-free (mean follow-up 30 months). DNA screening results in one affected family are presented. DNA analysis allowed the recognition of one apparently unaffected individual at risk as MEN 2A gene carrier. One family member at risk was scored as not carrying the gene and may be excluded from further screening.

Testosterone treatment of men with idiopathic hemochromatosis.

Patients with chronic liver disease usually exhibit low plasma levels of testosterone with loss of libido and potency; this is also valid in male patients suffering from idiopathic hemochromatosis (IHC), in whom nowadays the diagnosis is made at an earlier age. Therefore, the effect of testosterone treatment was studied in 10 patients with IHC. After the application of 250 mg testosterone enanthate i.m., the plasma testosterone (from 2.4 +/- 1.9 to 20.1 +/- 7.4 ng/ml) and estradiol (from 17.4 +/- 6.3 to 38.5 +/- 14.2 pg/ml) levels increased significantly. The rise of estradiol was in the range of controls and smaller than reported in other chronic liver diseases. In a long-term study, 250 mg testosterone enanthate was given 4-weekly for 33-96 months to 5 patients with IHC. General well-being, libido, and potency recovered almost immediately. Over a treatment period of 27.3 patient years, symptoms of hyperestrogenism (gynecomastia) or (portal vein) thrombosis were not seen, both of which had been described in patients with alcoholic liver cirrhosis. There was no deterioration of liver function. The effect of testosterone treatment on the patients' well-being and plasma hormone concentrations remained unchanged over the whole period of testosterone treatment. Thus, in male patients with IHC and lowered plasma testosterone, treatment with testosterone enanthate may be instituted. Because of the positive effects on general well-being, liver regeneration capacity, and potency, testosterone should especially be administered to younger subjects suffering from IHC.

Glucocorticoid receptors in rheumatoid arthritis.

OBJECTIVE: Increasing evidence suggests that there is a close interrelationship between the immune system and the hypothalamic-pituitary-adrenal axis. One way these systems are linked is through specific receptor proteins for glucocorticoid hormones in lymphocytes. We sought to determine whether the levels of these receptors differ in patients with rheumatoid arthritis (RA), compared with levels in healthy subjects. METHODS: We determined the density and affinity of lymphocyte glucocorticoid receptors, as well as basal cortisol levels, in 90 patients with active RA and in 200 healthy controls, using a whole cell binding assay. RESULTS: The number of glucocorticoid receptors in RA patients was significantly lower than in controls (mean +/- SD 2,144 +/- 500 per cell versus 5,619 +/- 1,373 per cell; P less than 0.001), whereas there were no differences in binding affinity or cortisol levels. Glucocorticoid receptor density did not correlate with inflammatory disease activity. CONCLUSION: Since glucocorticoids are potent immunosuppressive agents, the decrease in their receptors suggests an impairment of the immune-hypothalamic-pituitary-adrenal axis in patients with RA.

Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia.

Adrenal tumors are being detected more frequently in consequence of the wider application of increasingly sensitive radiological investigation techniques. According to the working hypothesis that more silent adenomas could develop from hyperplastic tissue areas under increased stimulation of the adrenal cortex, heterozygous and homozygous patients with congenital adrenal hyperplasia (CAH) were studied. A high incidence of adrenal masses, nearly 82% in homozygous and 45% in heterozygous patients, was found. There was no correlation between tumor size and serum 17-hydroxyprogesterone concentrations. These tumors are, therefore, probably silent adenomas. On the basis of these results, CAH should always be ruled out in the case of incidentally detected adrenal masses. Since CAH is a relatively frequent disease, and the adrenal carcinoma belongs to the rarest malignant tumors, a malignant transformation of these tumors seems to be unlikely.

The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone.

BACKGROUND: Suppression of pituitary-adrenal function is a well-known consequence of glucocorticoid therapy, manifested principally by decreased corticotropin secretion. To determine the degree of suppression of pituitary-adrenal function in patients treated with different doses of synthetic glucocorticoid medication for different periods, we measured the pituitary-adrenal response to the administration of exogenous human corticotropin-releasing hormone (CRH). METHODS: We studied 279 patients who were receiving daily therapy with 5 to 30 mg of prednisone or its equivalent to treat various chronic diseases, principally collagen vascular disorders, and 50 normal subjects. Therapy ranged in duration from 1 week to 15 years. Stimulation tests using 100 micrograms of CRH as a bolus injection were performed in the morning, 24 hours after the most recent dose of glucocorticoids. In 61 patients an insulin hypoglycemia test, thought by many to be the reference standard, was also performed to assess the reliability of the CRH results. RESULTS: After the administration of CRH, 43 patients had no increase in plasma concentrations of corticotropin and cortisol. The response was blunted in 133 patients and normal in 103. There was poor correlation between the plasma cortisol response after the administration of CRH and the dose or duration of therapy or the basal plasma cortisol concentration. Although plasma cortisol concentrations after stimulation with CRH were generally lower than those after insulin administration, there was a significant correlation between the plasma cortisol responses to the two stimuli (r = 0.82). CONCLUSIONS: Pituitary-adrenal function in patients treated with synthetic glucocorticoids cannot be reliably estimated from the dose of glucocorticoid, the duration of therapy, or the basal plasma cortisol concentration. In such patients, testing with CRH is nearly as useful as insulin hypoglycemia testing in the assessment of pituitary-adrenal function.