Severity Of Thyroid Dysfunction Research Articles

Endocrine Adverse Events Related To Immune Checkpoint Inhibitor Treatment: Relationship Between Antibodies and Severity of Thyroid Dysfunction.

The purpose of this study was to identify predictive and risk factors for the development of immune-related endocrinopathies and to analyze the incidence and characteristics of immune-related endocrinopathies in our population Design: A retrospective, single-centre cohort carried out at Gregorio Marañón Hospital between January 2018 -December 2019. A total of 163 patients were enrolled. In January 2018 and December 2019, we treated patients who underwent ICI treatment in the Medical Oncology Department of General University Hospital Gregorio Marañón, a tertiary care public hospital in Madrid, as part of an observational, retrospective, single-center cohort study. Endocrinopathies were diagnosed in 19.5% of the patients (n=32). The tumours with the highest incidence of endocrinopathies were non-small cell lung cancer (25,9%), kidney cell cancer (25%) and hepatocarcinoma (20%). Among the 32 patients who developed endocrinopathy, 18,8%, 19,13%, and 21,28% received anti-CTLA-4, anti-PD-1 and anti-PDL-1, respectively. Thyroid dysfunction was the most frequent endocrinopathy (12,8%). A higher percentage of patients with negative antiTPO and antiTG antibodies developed G1 hypothyroidism compared to patients with positive antibodies who developed a higher proportion of G2 hypothyroidism. The presence of an initial phase of thyrotoxicity was not related to greater severity. We observed longer progression-free survival in patients who developed thyroid dysfunction. Pre-existing antibodies were independently associated with endocrinopathies. Moreover, our study let us conclude that the presence of thyroid autoantibodies may be related to its severity. It is important to determine anti-thyroid antibodies prior to the start of immunotherapy as a risk factor for thyroid dysfunction, which in turn is a prognostic marker.

Outcome of critically ill patients with non-thyroidal illness

Background: During period of critical illness, there are diverse alterations in the hypothalamus-pituitarythyroid (HPT) axis. This diversity in critically ill patients and the etiological relationship between underlying disease and non-thyroidal illness (NTI) is poorly understood. The aims of this study were to examine the features of NTI and outcomes in critically ill patients admitted in Critical Care Medicine (CCM) Department, BIRDEM General Hospital.
 Methods: A total of 86 patients admitted to CCM department, BIRDEM General Hospital during the period of July to December 2015 , having nonthyroidal illness, detected by thyroid function tests during ICU stay were enrolled in this study. All patients discharged from hospital were followed up for a period of 6 months. Patients with known thyroid diseases or taking medications that affect thyroid function were excluded. Condition at hospital discharge and mortality in the ICU or later at home after discharge within next 6 months was assessed as outcomes.
 Results: Mean age of the study subjects was 63.87(±13.5)years and 45(52.3%)of the study subjects were female. Most of the study subjects had diabetes (84.88%) and hypertension (82.55%).Mean (±SD) of FT3 (pmol/l), FT4(pmol/l), TSH (uIU/ml) were 2.85(±1.35),12.74(±8.17) and 2.81(±8.57)respectively. Among the total study subjects 44.18% patients died in ICU and 2.32% patients after shifting to ward. Among the patients having pneumonia, Myocardial Infarction(MI) /Arrhythmia, Stroke, Sepsis and Gastrointestinal disease, 50.94% 51.02%, 56.0%,53.85%,37.50% died in hospital (ICU or after shifting toward).The 46 patients ,who were discharged from hospital were followed up for next 6 months.
 Conclusion: NTI is a transient adaptive response affecting individuals with acute and chronic illness and is more common among patients admitted in intensive care unit (ICU). The prognosis of patients having NTI depends on severity of thyroid dysfunction.
 Birdem Med J 2021; 11(1): 47-51

Treatment of Thyroid Dysfunction and Serum Lipids: A Systematic Review and Meta-analysis.

Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia. The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus from 1970 through April 5, 2018. Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism. Pairs of independent reviewers extracted data and appraised studies. Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI]: 37.99, 51.02), low-density lipoprotein cholesterol (LDL-C) by 31.13 mg/dL (95% CI: 24.33, 37.93), high-density lipoprotein cholesterol (HDL-C) by 5.52 mg/dL (95% CI: 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI: 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI: 22.67, 29.57), and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI: 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI: -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI: -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI: -5.67, -2.61), TGs by -7.25 mg/dL (95% CI: -36.63, 17.87), apo A by -12.59 mg/dL (95% CI: -17.98, -7.19), apo B by -33.96 mg/dL (95% CI: 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI: -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration. Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism.

SAT-465 Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis: Diagnosis or Distraction?

In 1966 a case of episodic encephalopathy with anti-thyroid antibody (ATAb) positive Hashimoto’s thyroiditis was first reported. Controversy persists regarding Hashimoto’s encephalopathy, now known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) and any relationship with ATAb. There is no literature supporting an etiologic role of ATAb in SREAT. Nor has there been correlation shown between ATAb titer and severity of thyroid dysfunction or SREAT(1).A 56 yo female was admitted to a community hospital three times with visual hallucinations and slurred speech. Brain MRI, LP and standard tests including C3/C4, folate, B12, ANA and ANCA were unrevealing. Thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were positive. Diagnosed with SREAT with relief of symptoms on high dose IV corticosteroids. Discharged on oral prednisone. Seven months later she began experiencing progressive proximal weakness of all extremities associated with exertional dyspnea, fatigue and weight gain. EMG studies indicated steroid-induced myopathy of the proximal extremities. After prednisone tapering, she was admitted to our institution with acute confusion, blurred vision, fever, tachycardia, tachypnea and hypoxemia.Examination showed Cushingoid features. Labs showed hyperglycemia, ANA (+), TPOAb (+), TgAb (+), low FreeT4, low T3, normal TSH and elevated IgG in the CSF. Brain MRI showed meningeal enhancement of parieto-occipital lobes and left tentorium. Empiric antibiotics started to cover infectious meningoencephalitis. Endocrinology consulted for iatrogenic Cushing’s syndrome with hyperglycemia, abnormal thyroid function tests (TFTs) with positive ATAb and evaluation for SREAT. We recommended tapering steroids and evaluation for infectious, autoimmune or paraneoplastic causes of encephalopathy, before presuming SREAT. Rheumatological and infectious work-up was negative. CT chest showed nodular densities and CT abdomen showed hepatic, splenic and right inguinal region masses. Biopsy of inguinal mass showed Diffuse Large B-cell Lymphoma confirmed on bone marrow biopsy. CSF flow cytometry was unrevealing, likely due to prior steroids. Leptomeningeal enhancement likely reflected leptomeningeal metastases. Treated with systemic R-CHOP, high dose MTX, intrathecal MTX, cytarabine and corticosteroid tapering. Complete remission was achieved with normalization of TFTs, resolution of her Cushingoid and encephalopathic features.This case illustrates SREAT as a diagnosis of exclusion. ATAbs may be positive in non-thyroid autoimmune disorders, other neurological conditions and 10-20% of the general population (2). B cell lymphoma with leptomeningeal metastasis caused encephalopathic features which improved with corticosteroids. Ascribing a diagnosis of SREAT led to delayed cancer diagnosis and treatment.

Thyroid dysfunction in beta thalassemia major patients

Background: Endocrinopathies are now amongst the common complications of thalassemia but determining the exact prevalence is difficult because of differences in age of first exposure to chelation therapy and the continuing improvement in survival in well-chelated patients. Hypothyroidism is the second most common endocrine disorder after hypogonadism, having been reported in 5.6% to 17% of patients. Material and Methods: The present study was conducted in Umaid hospital attached to Dr S.N. Medical College, Jodhpur. 112 children were enrolled in the study and thyroid function tests along with serum Ferritin levels were done for all the subjects. Results: Out of a total of 112 children, 82 were Euthyroid (73.2%) and 30 were Hypothyroid (26.8%). The mean serum Ferritin, serum TSH, serum Free T4 and serum Free T3 in Euthyroid children were 1975.4 ± 706.2(ng/ml), 3.23 ± 0.93(μIU/ml), 12.8 ± 2.3(pmol/l) and 6.12 ± 1.4(pmol/l) respectively. Whereas in Hypothyroid children the mean serum Ferritin, serum TSH, serum Free T4 and serum Free T3 were 2842.9 ± 1095.2(ng/ml), 7.05 ± 1.91(μIU/ml), 10.55 ± 2.0(pmol/l) and 4.49 ± 1.2(pmol/l) respectively. Conclusion: Prevalence , severity of thyroid dysfunction in thalassemics is variable and regular follow up is the key. Assessment of thyroid function should be done annually from the age of 9 or earlier if patient is clinically symptomatic.

Thyroid Function in Chronically Transfused Children with Beta Thalassemia Major: A Cross-Sectional Hospital Based Study.

Background Thalassemia is the most common genetic disorder worldwide. Use of iron chelators has improved survival but endocrine complications have become more frequent. The frequency of hypothyroidism in Beta Thalassemia Major (BTM) children ranges from 6 to 30 %. Thyroid dysfunction mainly occurs by gland infiltration, chronic tissue hypoxia, free radical injury, and organ siderosis. Objectives (a) To evaluate the thyroid function status in chronically transfused children with BTM, in the first and second decade of life and (b) to study the influence of factors like duration and amount of blood transfusions, serum ferritin level, and iron chelation therapy on thyroid function. Methodology BTM children, 3 years old and above, on regular blood transfusions with serum ferritin > 1500 mcg/l were included in the study. Thyroid function and ferritin assessment was done using ELISA kits. Autoimmune thyroiditis was ruled out by antithyroid peroxidase and antithyroglobulin antibody testing. Results A study population of 83 children consisted of 49 boys (59%) and 34 girls (41%). 4.8% of the children had evidence of subclinical hypothyroidism. Among them two belonged to the first decade and the other two to the second decade of life. Mean TSH, FT4, and ferritin values among children with thyroid dysfunction were 6.38 ± 0.83 mIU/ml, 1.08 ± 0.45 ng/dl, and 3983.0±1698.30 ng/ml, respectively. The severity of thyroid dysfunction was statistically significantly associated with higher serum TSH values in children in the second decade of life with a p value = 0.001. No other significant correlation was found between oral chelation, amount and duration of blood transfusion, or serum ferritin levels. Conclusion Subclinical hypothyroidism was the thyroid dysfunction observed in our study. Regular blood transfusions with adequate chelation may decrease incidence of thyroid dysfunction.

EUTHYROID SICK SYNDROME AND CYTOKINE IMBALANCE IN PATIENTS WITH FUNCTIONAL DYSPEPSIA

The article presents the results of the study assessing the role of thyroid dysfunction and cytokine imbalance in the pathogenesis and manifestations of functional dyspepsia. We found that 31 % of the patients with functional dyspepsia had low serum triiodothyronine (T3) and/or free serum thyroxine (T4) levels as well as normal or mildly reduced serum TSH levels, thus confirming the presence of euthyroid sick syndrome in such patients. These changes in thyroid hormone levels were more frequent in postprandial functional dyspepsia than in epigastric pain syndrome. Moreover, the functional dyspepsia group was found to have elevated mean anti-TPO levels as compared with the controls. Thyroid imbalances were associated with mildly elevated pro-inflammatory (TNF-α, IL-1 ß, IL-6, IL-8) cytokine levels and low levels of serum anti-inflammatory IL-10 cytokine as compared with the healthy subjects. Along with this, hypercytokinemia was less pronounced in functional dyspepsia than in peptic ulcer. We obtained evidence of a strong correlation between clinical manifestations of functional dyspepsia and the severity of thyroid dysfunction. Positive correlation was found between T3, free T4, TNF-α, IL-1 ß, IL-6 and IL-8, while pro-inflammatory IL-10 cytokines were negatively correlated with free T4 leväs. Our findings suggest that thyroid dysfunction and regulatory cytokines play a significant role in the pathogenesis and manifestations of functional dyspepsia and represent objective markers of disease severity.

Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer

ABSTRACTPurpose: Drugs that blockade interaction between programmed cell-death protein 1 (PD-1) and its ligand (PD-L1) are promising. Immune-related adverse events (irAEs) might be associated with favorable clinical outcomes, and thyroid dysfunction is one of the most common irAE. We evaluated the association of thyroid dysfunction during PD-1 blockade with the treatment efficacy in patients with non-small cell lung cancer (NSCLC).Experimental Design: A total 58 patients with stage IV NSCLC treated with PD-1 blockade were enrolled. Patients were categorized into thyroid dysfunction and euthyroid groups. Overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Patients, tumor, and medication factors were adjusted using Cox proportional hazard modeling. Objective response rate (RR) and durable control rate were assessed according to the severity of thyroid dysfunction.Results: OS [median 118.0 (73.0-267.0) vs. 71.0 (28.0-160.0) days, log-rank P = 0.025] and PFS [118.0 (73.0-267.0) vs. 61.0 (28.0-130.0), log-rank P = 0.014] were longer in the thyroid dysfunction group. After adjustment, thyroid dysfunction was an independent predictive factor for favorable outcome [adjusted HR = 0.11 (95% CI) 0.01-0.92 for overall death; 0.38 (0.17-0.85) for disease progression]. The severity of thyroid dysfunction was associated with durable control rate (P for trend = 0.008).Conclusions: Thyroid dysfunction during PD-1 blockade is associated with treatment response and could provide supplementary information for immune monitoring in patients with advanced NSCLC.

Particularities of endothelial dysfunction in hypothyroid patients.

It is well known that hypothyroidism promotes the premature onset of subclinical atherosclerosis. This condition is defined by endothelial dysfunction (ED) and increased arterial stiffness (AS) and leads to augmentation of peripheral vascular resistance. To assess the presence and severity of ED and to follow its evolution under therapy in three groups of hypothyroid patients, we used three different noninvasive methods: carotidian intima-media thickness (IMT), flow mediated vasodilatation (FMD), and AS. The study group consisted of 56 young, hypothyroid women without associated cardiovascular pathology or risk factors for atherosclerosis. We selected our patients in order to have normal IMT (< 0.9 mm) and assessed the basal diameter of the brachial artery and the alterations of FMD and of AS parameters: pulse wave velocity (PWV) and augmentation index (AIx). We found, in all patients, a reduced basal diameter of brachial artery, pathological patterns of FMD, and increased values of PWV and AIx, compared to controls, in relation with the severity of thyroid dysfunction. We documented an improvement of ED after therapy with L-thyroxin. ED, documented in hypothyroid patients by means of three noninvasively methods, was strongly related to the severity of thyroid disease. We detected, in all three subgroups, significant alterations of FMD and AS, even in the absence of structural changes, documented by a normal IMT. ED improved consistently after restoring the euthyroid state.

Incidence of thyroid dysfunction in renal cell carcinoma (RCC) patients treated with pazopanib in prospective clinical trials.

4633 Background: Pazopanib is a small molecule, selective, multi tyrosine kinase inhibitor (TKI), targeting vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R). Pazopanib is approved for the treatment of advanced RCC and is given by oral daily dosing. Other TKIs for this indication induce thyroid dysfunction in up to 85% of patients (pts) (Rini, B 2007). The incidence and severity of thyroid dysfunction were explored in pazopanib-treated pts participating in 3 trials, where thyroid function tests were systematically assessed. Methods: Thyroid function data from 578 RCC pts participating in trials VEG102616 (phase II), VEG105192 (phase III), and VEG107769 (phase III extension) were analyzed. Serum TSH values were collected at baseline and every 12 weeks. Free T3 and T4 were assessed at baseline and when TSH was abnormal during treatment. Results: In 578 pts, the incidence of elevated TSH at baseline (>5 MU/L) was 37 (6%).167 (29%) pts had a TSH value of >5 MU/L during treatment; 97 (17%) pts had TSH values of >5-10 MU/L during treatment; 45 (8%) pts had TSH values of >10-20 MU/L, and 25 (4%) pts had TSH values of >20 MU/L. Hypothyroidism (TSH >5-10 MU/L and T4 <LLN) was observed in 19 (3%) pts. Hypothyroidism with TSH >10 MU/L and T4<LLN was diagnosed in 15 (3%) pts. Hyperthyroidism, defined as TSH <0.3 MU/L and T4>ULN, was seen in 8 (1%) pts. Thyroid replacement therapy was received by 20 (3%) pts with a TSH elevation. Hypothyroidism was reported as an AE in 26 (4%) pts (15 Grade 1, 10 Grade 2 and 1 unknown grade) by the investigators. Thyroid dysfunction was never reported as a severe adverse event in any pt. Conclusions: In clinical trials, pazopanib, the most recently approved treatment for advanced RCC, lead to a very low incidence of thyroid dysfunction. The low rate of hypothyroidism may partly explain the low incidence of fatigue (19%) and asthenia (14%) with pazopanib (Sternberg 2010), given these conditions can result from hypothyroidism. As fatigue has a profound detrimental effect on HRQoL in RCC pts (Larkin 2010), this data should be considered when making clinical treatment decisions in pts with advanced RCC.

Sunitinib-related thyroid dysfunction: A single-center retrospective and prospective evaluation

3092 Background: Sunitinib is a multi-target tyrosine kinase inhibitor with anti-angiogenic and anti-proliferative activity mediated by signal blockade of VEGFR1/2, KIT, PDGFRα/β, and FLT-3. Phase II/III trials have demonstrated efficacy of the oral agent in Imatinib-resistant GIST and advanced renal cell cancer (RCC). We observed several cases of thyroid dysfunction in GIST during treatment with sunitinib suggesting that the drug may be associated with hypothyroidism. We therefore assessed the incidence and severity of thyroid dysfunction in cancer patients treated with sunitinib. Methods: Thyroid function (serum TSH, T3 and free thyroxin index) and thyroid antibodies (anti-TPO, -Tg and TSH-R-Ab) were evaluated retrospectively in a cohort of patients with GIST in a Phase III trial and in an expanded access program (1st part of the investigation) and in a prospective cohort of RCC and GIST patients treated in the framework of expanded access programs (2nd part). Sunitinib was given at a daily oral dose of 50 mg 4 weeks on, 2 weeks off. Thyroid parameters were assessed on days 1 and 28 of each treatment cycle in the prospective cohort. We report here the first TSH results, the full data set will be available at ASCO. Results: We identified a total of 46 patients who received sunitinib, and 33 of these patients were evaluable for thyroid function. 14 patients were analyzed retrospectively (all GIST), 19 patients prospectively (8 GIST, 11 RCC). 7 of these 19 patients (37%) showed an elevated TSH (&gt;5 mIU/L) during treatment. In the retrospective analysis of 14 patients with a median treatment duration of 44 weeks, 8 patients (57%) had developed hypothyroidism. All patients with GIST in randomized Phase III trial remaining under active treatment with sunitinib for 58–80 weeks show an increased TSH (up to 83 mIU/L) during the course of treatment, requiring hormone substitution. In a cohort of 11 patients with RCC, after 6 weeks of treatment, 3 patients already have an increased TSH. Conclusions: Sunitinib is associated with a high incidence of thyroid dysfunction which requires further study. The mechanism by which Sunitinib induces thyroid dysfunction is yet unclear. No significant financial relationships to disclose.

Correlation between severity of thyroid dysfunction and renal function

Renal function is profoundly influenced by thyroid status; however, this has not been studied in detail in human subjects. The purpose of the present study was to determine the relationship between renal function and thyroid status before and after treatment for hypothyroidism and hyperthyroidism, respectively. In 37 consecutive hypothyroid and 14 hyperthyroid patients renal function as measured by plasma creatinine and glomerular filtration rate (GFR) [based on the modification of diet in renal disease (MDRD) formula] was determined before treatment and after regaining euthyroidism. Renal function improved significantly during treatment of hypothyroidism and decreased during treatment of hyperthyroidism. There was a strong correlation between the change in thyroid status determined as the ratio log(10)(fT4 post-treatment/fT4 pretreatment) and the change in renal function as a result of therapy expressed as serum creatinine (r(2) = 0.81, P < 0.0001) and estimated GFR (0.69, P < 0.0001). The kidney is an important target of thyroid hormone action.

The development of Graves' disease and the CTLA-4 gene on chromosome 2q33.

Case-control studies suggest that the CTLA-4 gene may be a susceptibility locus for Graves' disease. The previously reported A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene was, therefore, investigated in a case-control (n = 743) and family-based (n = 179) dataset of white Caucasian subjects with Graves' disease. The relationship between CTLA-4 genotype and severity of thyroid dysfunction at diagnosis was also investigated. An increase in frequency of the G (alanine) allele was seen in Graves' patients compared with control subjects (42% vs. 31.5%, respectively; corrected P<0.0002; odds ratio = 1.58), and a significant difference in the distribution of GG, GA, and AA genotypes was observed between the groups (chi2 = 21.7; corrected P<0.00003). Increased transmission of the G allele was seen from heterozygous parents to affected offspring compared to unaffected offspring (chi2 = 5.7; P = 0.025). Circulating free T4 concentrations at diagnosis were significantly associated with CTLA-4 genotype (F = 3.26; P = 0.04). These results support the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders such as Graves' disease.

A QUANTITATIVE ASSESSMENT OF THYROID HISTOPATHOLOGY OF HERRING GULLS (LARUS ARGENTATUS) FROM THE GREAT LAKES AND A HYPOTHESIS ON THE CAUSAL ROLE OF ENVIRONMENTAL CONTAMINANTS

Thyroids from 213 adult herring gulls of both sexes were collected during incubation from nine colonies in the Great Lakes basin of eastern North America between 1974 and 1983, and from a single colony in the Bay of Fundy from 1977 to 1982. Qualitative and quantitative histological assessment revealed that the majority of the gulls from the Great Lakes basin suffered from goiter. These thyroids had a greater mass than those from the Bay of Fundy, and were microfollicular and frequently hyperplastic. The histopathology was similar to that previously observed in Pacific salmon from the Great Lakes. These findings are consistent wit a forage fish-borne goitrogenic etiology other than, or in addition to, iodine deficiency. Temporal and spatial differences in the severity of thyroid dysfunction are consistent with the hypothesis that polyhalogenated hydrocarbons are responsible for the goiter development and thyrotoxic effects observed in herring gulls from the Great Lakes area.

Incidence of hypothyroidism following multimodality treatment for advanced squamous cell cancer of the head and neck.

The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clinical evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck--particularly those patients having neck dissections or total laryngectomies--have routine thyroid function studies performed following the cessation of treatment.