Clinical and immunological studies on patients with Graves' disease preoperatively treated with corticosteroids and iodides

The purpose of this study was to evaluate the acute effects of corticosteroid and iodide preoperative therapy in patients with Graves' disease in terms of thyroid function and immunological parameters. The above combination was prescribed for 4 patients who had experienced severe side effects from antithyroid drugs (ATD) in order to reduce the possibility of post-thyroidectomy thyroid storm. Corticosteroids were employed daily for four days, and iodides were given daily for two weeks prior to thyroidectomy. The free T3 values decreased rapidly to euthyroid levels following the administration of both drugs, although the free T4 values were still much higher than normal in 3 of the 4 patients at the time of surgery. By comparison, 3 of 8 patients treated with ATD also had thyroid hormone levels above normal. Studies of lymphocyte subsets revealed that the percentage of helper T cells was significantly less in the corticosteroid-iodide treatment group than in the control and ATD groups. It is thus possible that postoperative thyroid storm might be prevented through corticosteroid-iodide therapy by virtue of the reduction of free T3 values to within the normal range by the time of surgery. The acute suppression of helper T cells was another results of this form of therapy observed.     

Thyroid function in children with nephrotic syndrome

The thyroid function of seven children with untreated nephrotic syndrome who had a normal serum creatinine concentration was compared with that of the same patients in remission and age-matched controls. There was a significant decrease in serum thyroxine (T₄), tri-iodothyronine (T₃) and thyroid-binding globulin (TBG) concentrations in untreated nephrotic children compared with the same patients in remission and age-matched controls. Most values for serum free T₄, free T₃ and thyroid-stimulating hormone (TSH) in the patients with nephrosis were within the normal range. However, the mean serum free T₄ and free T₃ concentrations were significantly (P<0.05) lower in the untreated patients than in the same patients in remission, and the mean serum TSH concentrations were significantly (P<0.05) higher in the untreated patients than in the same patients in remission. There were massive urinary losses of T₄, T₃, TBG. free T₄ and free T₃ in the untreated nephrotic children compared with the same patients in remission and age-matched controls. The daily urinary protein excretion showed a positive correlation with the urinary T₄, T₃, free T₄, free T₃ and TBG excretion. Furthermore, the urinary protein excretion showed a negative correlation with the serum T₄, T₃, free T₄, free T₃ and TBG levels. There was a negative correlation between serum albumin and serum TSH. These findings provide evidence of mild hypothyroidism in children with untreated nephrotic syndrome, partly because of losses of T₄, T₃, free T₄, free T₃ and TBG into the urine.     

Reduction in Triiodothyronine Levels Following Modified Fontan Procedure

Diminished cardiac function is a common manifestation following the modified Fontan procedure. Since thyroid hormone has important effects on cardiovascular function, the present study was undertaken to evaluate changes in thyroid hormone levels following this operation. A control group consisting of children undergoing open heart procedures other than a Fontan procedure was also evaluated. Serum total and free triiodothyronine (T₃), total and free thyroxine (T₄), thyroid stimulating hormone (TSH), and thyroglobulin were measured by immunoassays. The Fontan group demonstrated an initial increase in free T₄, while free T₃, total T₃, total T₄, TSH, and thyroglobulin were reduced. Over the subsequent days, free T₄ decreased to below the preoperative value. By the fifth and eighth postoperative days, free T₃, total T₃, free T₄, and total T₄ remained reduced, while TSH and thyroglobulin began increasing toward the preoperative levels. The control group also demonstrated decreases in free T₃ and TSH. However, these values had returned to baseline by the fifth postoperative day. The results indicate that children undergoing open heart surgery have suppression of the pitultary-thyroid axis, and that this is prolonged in patients undergoing Fontan procedure. The decreased levels of T₃ following Fontan procedure may have adverse effects on the recovery of patients undergoing this operation. (J Card Surg 1994;9:322–331)     

Coronary artery bypass surgery in patients with angina pectoris and hypothyroidism.

The treatment of hypothyroidism in patients undergoing coronary artery bypass surgery is a difficult clinical problem. To determine perioperative thyroid replacement therapy in patients with hypothyroidism, plasma total thyroxine (T4), total triiodothyroxine (T3), free T4, free T3 and thyroid-stimulating hormone levels were measured preoperatively and at 1, 2, 3, 7, and 14 days after operation in 9 patients with hypothyroidism and were compared with levels in 14 patients with normal thyroid function who underwent coronary bypass surgery. In the normal control group, total T4 decreased to its lowest level on the 1st postoperative day and then increased gradually to the preoperative level at 7 days. Total T4 remained within the normal range throughout the entire postoperative course. In 6 patients with hypothyroidism who were treated with thyroid hormone before surgery, total T4 decreased immediately after operation and only increased after starting thyroid replacement therapy. In 3 hypothyroid patients without prior thyroid replacement, total T4 showed a change similar to patients in the control group but remained below the normal range until starting thyroid replacement therapy. Coronary bypass surgery was performed safely in patients with hypothyroidism. Preoperative thyroid replacement with suboptimal doses was safe in patients with severe hypothyroidism. Adequate postoperative thyroid replacement was achieved in all patients without complications.     

A comparative evaluation of the surgical and radioiodine treatments for Graves’ disease

Radioactive iodine treatment is currently the most popular treatment modality for hyperthyroidism in many patients of the world. In Japan, however, a considerable number of patients with hyperthyroidism have undergone successful surgery. To elucidate the advantages and disadvantages of surgical and¹³¹I treatment, the thyroid function of 66 patients from each group was compared, 5 to 8 years after treatment. None of the surgically treated patients had been reoperated upon on, whereas 12 (18 per cent) of the patients treated with¹³¹I required 2 or more doses. The number of patients with normal ranges of serum T₃, T₄ and TSH values was almost identical: 33 (50 per cent) of the postoperative patients and 31 (47 per cent) of the post-irradiated patients. In the surgically treated group, there was no tendency for hypothyroidism to develop with the passage of the time. However, although the distribution of T₃ and T₄ in the normal control and postoperative groups showed a normal bell-shaped distribution, the post-irradiated group did not exhibit this distribution. The normal control group and the postoperative group showed positive correlations of T₃ and T₄ but the post-irradiated group did not (p<0.05). When the titers of antithyroglobulin and antimicrosomal antibodies prior to therapy were compared with those following therapy, they had decreased in 41 per cent and 76.8 per cent, respectively, of the postoperative cases, but in only 24.2 per cent and 45.5 per cent of the post-irradiated cases.     

Hypothyroidism in infants with nephrotic syndrome

Thyroid function indices were studied in five children with nephrotic syndrome in the 1st year of life. Four had primary hypothyroidism as defined by low serum free tri-iodothyronine (FT₃) and free thyroxine (FT₄), and high serum thyroid-stimulating hormone (TSH) levels. One patient with low serum FT₃ and FT₄ had a normal TSH level. T₄ replacement therapy lowered TSH to normal levels in all four patients and normalized FT₄ in three of them. There were no significant changes in serum FT₃ levels. Adrenal function was studied in three patients, none had adrenal calcification or hypoadrenocorticism. This study supports the existence of a hypothyroid state in some infants with nephrotic syndrome. Routine thyroid screening and early replacement therapy is recommended.     

Thyroid function in patients with acute renal failure

Thyroid function was evaluated in a group of 36 patients with acute renal failure (ARF) during the oliguric/anuric, polyuric and postpolyuric phase. Serum thyroxine (T₄) and triiodothyronine (T₃) concentrations were significantly decreased in the oliguric/anuric phase, as compared with the mean values obtained in the postpolyuric phase and with controls.In contrast to T₃ and T₄, the concentration of serum reverse triiodothyronine (rT₃) was elevated in the oliguric/anuric phase and normal in the polyuric phase. The sephadex-T₃-binding index (T₃I) was significantly increased in oliguric/anuric patients and in the polyuric phase. The levels of serum thyreotropin were significantly elevated during all phases of ARF as compared with the controls. From the results obtained it is concluded that abnormal peripheral metabolism of T₄ seems to be the primary cause of altered plasma concentrations of thyroid hormones in patients with ARF.     

Effect of preoperative iodine in patients with Graves'' disease controlled with antithyroid drugs and thyroxine.

Thirty-four patients with Graves' disease, first rendered euthyroid with antithyroid drugs (ATD) then given supplementary thyroxine (T4), were randomly allocated to three treatment groups. In Group I ATD and T4 were stopped 10 days before partial thyroidectomy and the patients were treated with Lugol's iodine alone. In Group II the patients were treated up to the time of operation with ATD and T4 alone. In Group III ATD and T4 were continued until the day of operation, but the patients also received 10 days' treatment with Lugol's iodine. Analysis of the results showed that pre-operative iodine therapy in patients with Graves' disease, already rendered euthyroid with ATD and T4, made no difference to the vascularity of the gland, operative blood loss or thyroid follicular size. Over a third of patients in Group I, treated with Lugol's iodine alone for 10 days pre-operatively, had subnormal levels of thyroid hormones at the time of operation and this was also the Group in which the complications of partial thyroidectomy tended to occur. It is concluded that the addition of iodine preoperatively is unnecessary in the patient who is already euthyroid on ATD and T4.     

Hypothalamic-pituitary thyroid abnormalities in children after renal transplantation

Patients with a successful renal transplant may have abnormalities in thyroid function. We evaluated serum thyroid hormone levels, serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH), and the circadian pattern of serum TSH in 18 children aged 6.6 – 19.4 years (median 12.6 years), 4.0 ± 2.9 years after renal transplantation. In 14 children, immunosuppressive therapy included methylprednisone [mean (± SD) 0.17 ± 0.05 mg/kg per day], while in 11 it included deflazacort (0.32 ± 0.1 mg/kg per day). Seven children were studied twice, under methylprednisone and again while on deflazacort therapy. Mean total and free thyroxine (T₄) values were significantly below the mean control levels (total T₄ 108.5 ± 21.5 vs. 118.7 ± 22.1 nmol/l, P <0.05 and free T₄ 14.4 ± 4.0 vs. 18 ± 4.9 pmol/l, P <0.001). Morning basal TSH levels were within the normal range. The mean TSH increment after TRH was 4.4 ± 3.5 mU/l, significantly lower than that of controls (10.8 ± 4.26, P <0.001). Of 7 patients on methylprednisone, 4 had nocturnal TSH surges below the normal range (95% confidence limits 47% – 300%); this occurred in 3 of 8 patients on deflazacort therapy. The TSH response to TRH was correlated with deflazacort dose. Patients on methylprednisone and deflazacort therapy had similar thyroid alterations. Our findings support the hypothesis that after renal transplantation some children have hypothalamic-pituitary thyroid abnormalities in which glucocorticoids may play a significant role. Received August 11, 1995; received in revised form and accepted December 6, 1995     

Two cases of hyperthyroidism induced by interferon-alpha therapy for renal cell carcinoma

Autoimmune thyroid disease is the result of a common side-effect of interferon-alpha (IFN-alpha) used to treat viral hepatitis C; but there have been few reports on thyroid disorders induced by IFN-a that was used to treat renal cell carcinoma. IFN-alpha therapy was conducted on two male patients, 75 and 44 years old, after radical nephrectomy. Six and five months, respectively, after this therapy, they complained of weight loss. Laboratory evaluation revealed hyperthyroidism; the thyroid stimulating hormone (TSH) level fell below normal; and the serum free T3 and T4 levels increased above normal values. Two months after the termination of IFN-alpha therapy, their thyroid hormone levels returned to normal without the help of antithyroid agents. In observational studies, thyroid dysfunction has been reported in 0.6 to 30% of the patients who had been treated with IFN-alpha. Careful observation is necessary to watch for the possible development of thyroid disorder during IFN-alpha therapy for renal cell carcinoma.     

A longitudinal assessment of bone loss in women with levothyroxine-suppressed benign thyroid disease and thyroid cancer

To determine if differeing degrees of levothyroxine (LT₄) suppression therapy for benign and malignant thyroid disease are associated with proportionately increased rates of bone loss, this longitudinal assessment of bone densitometry changes (single-photon and dual-photon absorptiometry) was conducted in three groups of subjects: 24 thyroid cancer patients who were treated with near-total thyroidectomy, radiodine ablation, and aggressive LT₄-suppression; 44 patients who were treated with more conservative LT₄-suppression for benign thyroid disorders; and 24 normal controls. Bone densitometry values were adjusted for age, weight, heigh, and menopausal status. The rates of bone loss in benign LT₄-suppressed patients were greater than those in controls at the midradius, distal radius, lumbar spine, and femoral neck. The rates of loss in the thyroid cancer patients were also greater than those in the controls at all four sites and greater than in the benign LT₄-suppressed patients at the midradius, distal radius, and femoral neck but not in the lumber spine. Rates of bone loss were not significantly correlated with LT₄ dose or with the serum level of T₄ or TSH. LT₄-suppression therapy for benign throid disease is associated with accelerated bone loss. More aggressive LT₄-suppression for thyroid cancer is associated with even greater bone loss, particularly in cortical bone regions. These risks must be weighed against the benefits of LT₄ therapy in individual patients.     

Hormone therapy as postoperative care in patients with differentiated thyroid cancer

TSH suppression therapy has been performed for 150 patients as postoperative care for differentiated thyroid cancer. L-thyroxine (LT4) was given in a dose of 2.1-4.8 micrograms/kg/day, per os. Serum thyroid hormone determinations were done after confirming that the drug had continually been taken for more than three months. Serum free T4 (FT4) values were elevated higher than the upper normal limits (1.9 ng/dl) in 127 of 150 cases (84.7%). In 100 cases of these, serum free T3 (FT3), reverse T3 (rT3) and TSH were estimated. In 98 cases (98%), serum FT3 was within the normal limits (3-6 pg/ml) and no correlation was found between values of FT4 and FT3. These serum rT3 values, however, were elevated higher than the normal range (13-43 ng/dl) in 41 cases (41%) correlating with FT4 values. Serum TSH, FT4 and FT3 showed no correlation with given LT4 doses. There was no correlation between the serum TSH and FT3. However, some correlation (r = -0.4046) was found between serum TSH and rT3 values. From these results the following conclusions were obtained: i) There must be some auto-regulating mechanisms to keep the serum FT3 values at the normal level by promoting a de-iodinating process from T4 to rT3 when serum T4 level increased, since rT3 has no hormone activity. ii) Administration of synthesized LT4 is safer and more adequately usable than synthesized L-triiodothyronine or desiccated thyroid, as the TSH suppression therapy, because the above mentioned autoregulating mechanism would take place.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anterior pituitary,thyroid, parathyroid and adrenal responses to subtotal thyroidectomy in patients with Graves’ disease

Changes in the serum levels of anterior pituitary, thyroid, parathyroid, and adrenal hormones following subtotal thyroidectomy in 31 patients with Graves’ disease were investigated. In 14 patients, rapid ACTH tests were performed on the preoperative and the first, third, and seventh postoperative days. Remarkable differences were not seen with regard to the changes in anterior pituitary hormones or cortisol, compared to those seen during general surgery. As to the thyroid hormones, the serum level of triioodothyronine (T₃) decreased markedly after surgery and fell to half that of the preoperative value on the first postoperative day. Thereafter, a low value of T₃ was maintained during the early postoperative period. Unlike T₃, the serum level of thyroxine (T₄) decreased gradually until the 7th post-operative day. The levels of both epinephrine and norepinephrine increased transiently during surgery, but the serum level of norepinephrine increased again on the third postoperative day. In the postoperative period, almost half the number of patients showed an inadequate cortisol response to rapid ACTH tests. It is suggested that the unique responses, such as the rise in serum norepinephrine or an inadequate response of cortisol to ACTH, or hypocalcemia, after subtotal thyroidectomy in patients with Graves’ disease is largely due to the rapid decrease of T₃ in the hypothyroid state, as was noted during the postoperative period.     

Alterations of thyroid hormone indices in acute renal failure and in acute critical illness with and without acute renal failure

The present study evaluated thyroid hormone indices of patients with acute renal failure without other systemic illnesses (n = 12), as compared to patients with critical illnesses in the presence (n = 16) and absence (n = 6) of acute renal failure. Abnormalities in the group with acute renal failure alone included decreased serum levels of total T4 and T3, and elevated levels of free rT3. Serum levels of free T4 by equilibrium dialysis and the enzyme immunoassay, T3 uptake ratios, TSH and total rT3 were normal. These findings are consistent with the presence of decreased binding of T4 and rT3 to their serum carrier proteins. Critically ill patients with acute renal failure differed in that they had lower total T4 and T3 levels and elevated T3 uptake ratio values. As in the group with acute renal failure alone, total rT3 levels were normal and free rT3 values were elevated. The group with critical illness alone differed only in that the total rT3 concentrations were elevated in all patients. The alterations of thyroid hormone indices in acute renal failure are similar to those of other nonthyroidal illnesses with the exception of the normal total rT3 levels. This suggests that the failing kidney or the metabolic consequences of uremia specifically affect rT3 metabolism.     

Thyroid function after peritoneal lavage with polivinylpyrrolidone-iodine solution in diffuse peritonitis

In 36 patients, intraoperative peritoneal lavage with PVP-iodine solution (26 patients) or with the iodine free chemotherapeutic agent Taurolin (10 patients) was performed because of peritonitis. Total iodine serum levels increased considerably after peritoneal lavage with PVP-iodine. In the early postoperative phase, the resorbed iodine was mostly present as iodide in serum. Iodine serum values returned to normal after 30 days. A decrease in T4 and T3 could be observed with a concomitant reciprocal increase of rT3 in the acute phase of peritonitis. Normalization of the thyroid hormone took place after 8 days. A stronger increase in T4 occurred temporarily in 2 of 5 patients known to have thyroid function disorders. These changes in thyroid hormone may also be considered as the consequence of the severe primary disease. Normalization of hormone values was clearly delayed after PVP iodine lavage. The possible risk of an iodine-induced thyrotoxicosis after intraperitoneal application of PVP-iodine is pointed out, and objections are made to using this therapy.     

Thyroid function after radiotherapy and laryngectomy for carcinoma of the larynx

Total levels of thyroxine (T₄) and thyroid-stimulating hormone (TSH) were measured in 37 patients who had previously had carcinoma of the larynx treated by radiotherapy and total laryngectomy with thyroid lobectomy. Ten percent of the patients had clinical features of hypothyroidism and 30% had total T⁴ levels below the lower limit of normal. A further 40% had results in the low normal range. Forty-four percent of patients had raised TSH levels, 90% of these having low or low normal T₄ levels. The histology of the thyroid gland was normal in all 37 patients. Attention should be given to preserving intact the vasculature of the contralateral thyroid lobe whenever it is necessary to remove the ipsilateral thyroid lobe during a laryngectomy. Proper postoperative assessment of thyroid gland function is desirable in all these patients to identity those at risk of hypothyroidism and to avoid unnecessary morbidity.     

Evaluation of perfusion modes on vital organ recovery and thyroid hormone homeostasis in pediatric patients undergoing cardiopulmonary bypass

The objectives of this study were: (i) to evaluate the effects of perfusion modes (pulsatile vs. nonpulsatile) on vital organs recovery and (ii) to investigate the influences of two different perfusion modes on the homeostasis of thyroid hormones in pediatric patients undergoing cardiopulmonary bypass (CPB) procedures. Two hundred and eighty‐nine consecutive pediatric patients undergoing open heart surgery for repair of congenital heart disease were prospectively entered into the study and were randomly assigned to two groups: the pulsatile perfusion group (Group P, n = 208) and the nonpulsatile perfusion group (Group NP, n = 81). All patients received identical surgical, perfusional, and postoperative care. Study parameters included total drainage, mean urine output in the intensive care unit (ICU), intubation time, duration of ICU and hospital stay, the need for inotropic support, pre‐ and postoperative enzyme levels (ALT [alanine aminotransaminase] and AST [aspartate aminotransaminase]), c‐reactive protein, lactate, albumin, blood count (leukocytes, hematocrit, platelets), creatinine levels, and thyroid hormones (thyroid stimulating hormone [TSH], FT₃[free triiodothyronine], FT₄[free thyroxine]). All patients survived the perioperative and postoperative periods. There were no statistically significant differences in either preoperative or operative parameters between the two groups. Group P, compared to Group NP, required significantly less inotropic support, had a shorter intubation period, higher urine output in ICU, and shorter duration of ICU and hospital stay. Lower lactate levels and higher albumin levels were observed in Group P and there were no significant differences in creatinine, enzyme levels, blood counts, or drainage amounts between two groups. TSH, Total T₃, Total T₄, and FT₃, FT₄ levels were markedly reduced versus their preoperative values in both groups. FT₃ and FT₄ levels were reduced significantly further in the nonpulsatile group both during CPB and at 72 h postoperation. The results of this study confirm our opinion that pulsatile perfusion leads to better vital organ recovery and clinical outcomes in the early postoperative period as compared to nonpulsatile perfusion in pediatric patients undergoing CPB cardiac surgery. The plasma concentrations of thyroid hormones are dramatically reduced during and after CPB, but pulsatile perfusion seems to have a protective effect of thyroid hormone homeostasis compared to nonpulsatile perfusion.     

Coronary artery bypass surgery in a patient with hypopituitarism]

Patients with hypopituitarism are prone to perioperative complications resulting from adrenal insufficiency or hypothyroidism. Coronary artery bypass grafting was performed safely in a 53-year-old woman with postinfarction unstable angina and hypopituitarism. Cortisol and thyroid hormone were administered to maintain normal adrenal and thyroid function during and after the operation. Hydrocortisone was administered intravenously the day before surgery and for 2 weeks postoperatively and then was administered orally. Perioperative replacement thyroxine therapy was administered to avoid acute myocardial ischemia. Optimal thyroid replacement was achieved after surgery. No perioperative complications were seen. The patient remains free of angina with postoperative cortisol and thyroid hormone replacement therapy.     

Serum triiodothyronine,bone turnover,and bone mass changes in euthyroid pre- and postmenopausal women

Summary Hyperthyroidism and thyroid hormone substitutive therapy with serum iT₃ in the normal range of values are known to lead to increased bone remodeling and loss of bone mass. We looked for a relationship between serum iT₃ and bone metabolic or bone mass parameters in 402 euthyroid women aged 44–60. In a group of 93 premenopausal women, a group of 309 postmenopausal women, and a group of 118 untreated postmenopausal women, serum iT₃ was higher in the women classified as having “high” bone turnover according to both alkaline phosphatases and hydroxyprolinuria values. In postmenopausal women, serum iT₃ corrected for thyroid binding globulin (TBG) (T_3c) was higher in those receiving no estrogen replacement therapy. In a longitudinal study (n=131), the rate of changes in lumbar bone mineral content was associated with changes in T_3c. A less favorable bone mass evolution was associated with an increase in serum T_3c, and inversely. Data suggest that the relationship of iT₃/bone metabolism is direct and not merely the consequence of estrogen induced changes in both iT₃ and bone metabolism. iT₃ should be explored at the bone cellular level as a possible mediator in bone metabolic changes occurring in menopause and many other clinical situations.