Rodolfo Fonte

Raised serum TSH levels in patients with morbid obesity: is it enough to diagnose subclinical hypothyroidism?

OBJECTIVE Morbid obesity (body mass index (BMI)> or =40 kg/m(2)) is associated with thyroid function disturbances, with a high rate of subclinical hypothyroidism (SH) being the most consistently reported. We evaluated the circulating thyroid function parameters in morbid obese patients and related the results to the presence of circulating thyroid antibodies (Thyr-Ab). DESIGN AND METHODS Morbid obese patients were consecutively enrolled (n=350). Two control groups were used: control group (CG)1, healthy normo-weight subjects (n=50); CG2, normo-weight patients with SH (n=56) matched for TSH with the obese patients with SH. Serum levels of free triiodothyronine (FT(3)), free thyroxine (FT(4)), TSH, antithyroglobulin antibodies, and antithyroperoxidase antibodies were measured in all patients. RESULTS i) Compared with CG1, obese patients having thyroid function parameters in the normal range and negative Thyr-Ab showed significantly higher serum TSH and lower free thyroid hormones levels, but a similar FT(4)/FT(3) ratio; ii) SH was recorded in 13.7% obese patients; iii) compared with CG2, obese patients with untreated SH had a significantly lower rate of positive Thyr-Ab (32.1 vs 66.1%; P<0.005); iv) no gender prevalence was observed in SH obese patients with negative Thyr-Ab; and v) the comparison of the untreated SH patients (obese and normo-weight) with CG1 demonstrated that in SH obese subjects, unlike normo-weight SH patients, the FT(3) levels were significantly lower. This resulted in a normal FT(4)/FT(3) ratio in SH obese patients. CONCLUSION Thyroid autoimmunity is not a major cause sustaining the high rate of SH in morbid obese patients. In these patients, the diagnosis of SH itself, as assessed by a raised TSH alone, appears questionable.

Interstitial laser photocoagulation for benign thyroid nodules: time to treat large nodules.

Interstitial laser photocoagulation (ILP) is a new therapeutic option for the ablation of non‐functioning and hyper‐functioning benign thyroid nodules. Amelioration of the ablation procedure currently allows treating large nodules. Aim of this study was to evaluate the therapeutic efficacy of ILP, performed according to a modified protocol of ablation, in patients with large functioning and non‐functioning thyroid nodules and to identify the best parameters for predicting successful outcome in hyperthyroid patients.

A hypoechoic pattern of the thyroid at ultrasound does not indicate autoimmune thyroid diseases in patients with morbid obesity

OBJECTIVE Thyroid ultrasound (US) scan is a valuable tool for diagnosing thyroid diseases. In autoimmune thyroid disease (AITD), an hypoechoic pattern of the thyroid at US is related to circulating thyroid antibodies (Abs). The aim of this study was to evaluate the diagnostic accuracy of thyroid US for the detection of AITD in patients with morbid obesity. DESIGN Thyroid US scans showing an hypoechoic pattern of the thyroid were collected from 105 morbid obese patients (body mass index (BMI) >40 kg/m(2)) and 105 non-obese patients (BMI<or=30 kg/m(2)). RESULTS A thyroid hypoechoic pattern at US was consistent with clinical/biochemical features of AITD in 90/105 (85.7%) non-obese patients and in 22/105 (20.9%) morbid-obese patients (P<0.0001). By performing a complete thyroid work-up, including clinical examination, thyroid morphology, serum hormones, and auto-Ab measurements, the discrepancy between the US pattern and the results of the thyroid Ab tests was justified in 6/15 non-obese patients, and only in 1/83 morbid obese patients. Thus, an unexplained hypoechoic pattern of the thyroid at US, defined as negative tests for thyroid Ab and absence of justifying thyroid disturbances, was found in 2/105 (1.9%) non-obese patients and in 68/105 (64.8%) morbid obese patients (P<0.0001). CONCLUSIONS Our results suggest that i) morbid obesity may affect thyroid morphology, and ii) an hypoechoic pattern of the thyroid at US, a well-established parameter for diagnosing AITD, has a poor diagnostic accuracy when patients with morbid obesity are taken into account.

Burkitt-like lymphoma infiltrating a hyperfunctioning thyroid adenoma and presenting as a hot nodule.

BACKGROUND Most solitary hyperfunctiong regions on thyroid scan consist of benign tissue. Here we report a patient with a Burkitt-like lymphoma that was infilterated into a region containing a hyperfunctioning nodule. SUMMARY A 56-year-old man was referred to our Endocrine Unit in May 2009 due to the incidental discovery of a large left thyroid lobe nodule by a computed tomography study. This had been performed to search for a primitive tumor in a patient with bone metastasis. He was clinically and biochemically thyrotoxic with no evidence of humoral thyroid autoimmunity. The nodule had a dyshomogenous appearance at neck ultrasonography, with multiple hypoechogenic areas and calcifications. (99m)-Technetium thyroid scintiscan revealed a hot nodule with suppression of the contralateral lobe. Fine-needle aspiration cytology indicated the presence of neoplastic cells not of thyroid origin. Remission of hyperthyroidism was obtained with methimazole, and the patient was submitted to left lobe thyroidectomy and istmectomy. Histological analysis of the surgical specimen led to a diagnosis of Burkitt-like large B-cell lymphoma harbored within a thyroid adenoma. After further staging, the final diagnosis was stage IV E Burkitt-like lymphoma with the involvement of the bone and the thyroid. This is the first description of an aggressive Burkitt-like lymphoma that infiltrated an hyperfunctioning thyroid adenoma, thus presenting as a hot nodule at thyroid scintiscan. In our patient there was no humoral or histological evidence of thyroid autoimmunity, thus suggesting a metastatic seeding of the lymphoma within the hyperfunctioning thyroid nodule. CONCLUSIONS Involvement of the thyroid gland by Burkitt-like lymphoma is extremely rare as is close localization of malignancy and a hyperfunctioning thyroid nodule. As highlighted by the present report, performing fine-needle aspiration cytology should be always considered in the clinical context of a metastatic disease of unknown origin or when there are ultrasonography signs suggesting malignancy, even when the nodule is hyperfunctioning.

Occurrence of medullary thyroid carcinoma, bronchial carcinoid tumor, and papillary thyroid carcinoma in a family bearing the RET G691S polymorphism.

RET mutations play an important role in the development of human neuroendocrine tumors. The prevalence of the RET polymorphism G691S of exon 11 is higher in patients with medullary thyroid carcinoma (MTC) as compared to the general population. A weak association between RET polymorphisms and sporadic papillary thyroid carcinoma (PTC) has also been described. We hereby describe the association of MTC, bronchial carcinoid tumor, and PTC in a familial setting. A 75-yr-old woman developed MTC 7 yr after successful treatment of a bronchial carcinoid. Serum calcitonin was 12.9 pg/ml with a peak response to pentagastrin (151.0 pg/ml). The patient underwent total thyroidectomy and a genetic mutational analysis of the RET gene. Histological evaluation confirmed MTC with no evidence of lymph nodes involvement. After thyroidectomy serum calcitonin was <2.0 pg/ml. A germline missense mutation at codon 691 in exon 11 of the RET gene was found. The mutational analysis was extended to the patient’s offspring, and her daughter was found to bear the G691S polymorphism of RET. Wild type RET gene was found in the son. The daughter, who showed a nodular goiter, autoimmune thyroiditis and normal serum calcitonin, also underwent thyroidectomy. Histologic examination of the thyroid revealed an incidental PTC. This is the first description of a bronchial carcinoid tumor occurring in association with MTC. The occurrence of apparently unrelated NET in the same subject, or within a family, should be regarded as a challenge for deeper investigations into the possible oncogenic role of this genetic alteration.

Serum negative autoimmune thyroiditis displays a milder clinical picture compared with classic Hashimoto's thyroiditis

BACKGROUND Despite high sensitivity of current assays for autoantibodies to thyroperoxidase (TPO) and to thyroglobulin (Tg), some hypothyroid patients still present with negative tests for circulating anti-thyroid Abs. These patients usually referred to as having seronegative autoimmune thyroiditis (seronegative CAT) have not been characterized, and definite proof that their clinical phenotype is similar to that of patients with classic chronic autoimmune thyroiditis (CAT) is lacking. OBJECTIVE To compare the clinical phenotype of seronegative CAT (SN-CAT) and CAT as diagnosed according to a raised serum level of TSH with negative and positive tests for anti-thyroid Abs respectively. METHODS A case-control retrospective study enrolling 55 patients with SN-CAT and 110 patients with CAT was performed. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, Tg Abs, and TPO Abs were measured in all patients. RESULTS Patients with SN-CAT displayed significantly lower mean levels of TSH (6.6±3.4 vs 10.2±9.8 μU/ml; P=0.009), higher mean FT4 levels (1.1±0.2 vs 0.9±0.2 ng/dl; P=0.0002), and similar FT3 levels when compared with CAT patients. Mean thyroid volume was significantly greater in patients with CAT when compared with SN-CAT patients (11.2±6.5 vs 8.1±3.7 ml; P=0.001). Logistic regression demonstrated that FT4 (0.123 (0.019-0.775); (P=0.026)) and thyroid volume (1.243 (1.108-1.394); (P=0.0002)) were significantly and independently related to the diagnosis (CAT/SN-CAT). Patients with SN-CAT had a similar prevalence of thyroid nodules and female gender but a lower prevalence of overt hypothyroidism (5.4 vs 20.9%; P=0.012) as opposed to patients with CAT. CONCLUSIONS These results suggest an autoimmune etiology of SN-CAT, which, however, seems to have a milder clinical course when compared with CAT.

Body Weight Changes in a Large Cohort of Patients Subjected to Thyroidectomy for a Wide Spectrum of Thyroid Diseases

OBJECTIVE Patients undergoing thyroidectomy often complain of weight gain. The aim of this study was to longitudinally evaluate body-weight changes in patients thyroidectomized for euthyroid and hyperthyroid conditions in order to identify predictive factors. METHODS Anthropometric data and thyroid function parameters were retrospectively reviewed for 267 thyroidectomized patients before and 40 to 60 days and 9 months after surgery. Presurgery diagnoses included benign (Graves disease, nodular toxic goiter, nodular nontoxic goiter) and malignant (differentiated thyroid cancer) conditions. RESULTS Mean preintervention weight of the entire study group significantly increased (P<.0001) 9-months after thyroidectomy, from 70.8 ± 16.0 to 72.5 ± 16.4 kg. Body weight increased in 156 (58.4%) patients, decreased in 59 (22.1%) patients, and remained stable in 52 (19.5%) patients. A multiple regression model was constructed by entering the percentage of body-weight change 9 months postsurgery as the dependent variable and age, sex, presurgery body mass index, percentage of weight change 40 to 60 days postsurgery, presurgery thyroid-stimulating hormone (TSH) level, TSH level 40 to 60 days postsurgery, TSH level 9 months postsurgery, thyroid disease driving thyroidectomy, and type of surgical intervention as the covariates. No significant relationship was found for any of the covariates tested, with the exception of percentage of body-weight change at 40 to 60 days postsurgery (correlation coefficient, 0.869; [95% confidence interval, 0.692 to 1.046; P<.0001]). CONCLUSION Thyroidectomy is associated with a significant increase in body weight, which is not limited to patients with Graves disease. Postsurgery TSH levels do not account for subsequent body-weight changes. Short-term changes (40 to 60 days postsurgery) in body weight are highly predictive of the outcome at 9 months, suggesting that early factors related to thyroidectomy per se might play a role.

MAXIMAL STIFFNESS EVALUATION BY REAL-TIME ULTRASOUND ELASTOGRAPHY, AN IMPROVED TOOL FOR THE DIFFERENTIAL DIAGNOSIS OF THYROID NODULES

OBJECTIVE The aim of the study was to evaluate the diagnostic performance of a new ultrasound elastography (USE) parameter based on the measurement of the percentage of maximal stiffness within a nodule as compared with the already established elastographic strain index (SI) and to investigate their diagnostic performance according to nodule size. METHODS The study included 218 nodules. Each nodule underwent conventional ultrasound (US), USE evaluation, and fine-needle aspiration cytology (FNAC). Thyroid nodules were further stratified into 4 subgroups (G) according to their size (G1, <1 cm; G2, 1-2 cm; G3, >3 cm). USE evaluation comprised the measurement of the percentage of the areas included in the region of interest corresponding to the maximal stiffness (% Index) and of the SI. RESULTS The % Index and of the SI were significantly higher in malignant than in benign thyroid nodules, and both measurements displayed a good diagnostic performance (SI sensitivity and specificity, 0.66 and 0.90, respectively; % Index sensitivity and specificity, 0.76 and 0.89, respectively). Compared with SI, the % Index was more informative, both in the whole group of thyroid nodules (odds ratio [OR], 18.68; 95% confidence interval [CI], 6.06 to 63.49; P<.0001 versus OR, 26.15; 95% CI, 8.01 to 102.87; P<.0001, respectively) and in the G1 and G2 subgroups. CONCLUSION The % Index is a stronger predictor of nodule malignancy than both the SI and the conventional US signs. This is particularly true in nodules smaller than 1 cm, which are more difficult to explore both by conventional US and FNAC.

Dilated cardiomyopathy: a possibly underestimated presentation of Cushing’s disease

Cushing’s disease caused by an ACTH secreting pituitary adenoma accounts for nearly 70% of all cases of nonpharmacological hypercortisolism in humans. Patients with hypercortisolism have a high rate of cardiovascular complications. Previous studies suggested that patients with Cushing’s disease, in spite of having been successfully treated, maintain an increased cardiovascular risk. This might not be the case for hypercortisolism-induced cardiomyopathy, which might have a more favourable outcome. A 49-year-old man was referred to our Endocrine Unit by the Department of Cardiology because of the incidental detection of enlarged adrenal glands at a CT scan of the chest. The patient had a 4-year history of hypertension and severe dilated cardiomyopathy with unaffected coronary arteries. Five months earlier, he had been entered a waiting list for heart transplantation. Ultrasound imaging of the heart, which was performed according to the guidelines of the American Society of Echocardiography, showed an eccentric hypertrophy of the left ventricle and a severe impairment of the ejection fraction (EF) (25%) calculated according to the Simpson’s methods. The patient also suffered from diabetes, and 6 years before, he had undergone a prosthetic replacement of the left hip for a nonseptic necrosis of the femoral head. At physical examination, the patient had the typical features of chronic hypercortisolism including thin skin and ecchymoses, red-purple striae on the abdominal skin, muscles hypotrophy as well as the typical moon face and buffalo hump. Laboratory findings (including low-dose and high-dose dexamethasone suppression tests) suggested a diagnosis of Cushing’s disease, which was confirmed by an MRI of the sella turcica showing a 6-mm pituitary adenoma. After the successful removal of the tumour by trans-sphenoidal surgery, a rapid fall of the serum cortisol level was observed. Glucocorticoid replacement therapy was started giving cortisone acetate (25 mg at 08:00 am and 12Æ5 mg at 04Æ00 pm). Antihypertensive and antidiabetic drugs were successfully withdrawn on postsurgical day 12. The EF improved from 25% presurgery to 42% at 6 and 54% at 9 months after surgery. Because of this marked improvement of his cardiac function, the patient was removed from the heart transplantation list. Written informed consent to the study was obtained. The impressive amelioration of cardiac function observed in our patient soon after hypercortisolism was cured, prompted us to review the literature for similar cases. To this purpose, we searched PubMed using the following key words: Cushing’s syndrome and hypercortisolism entered together with heart failure and dilated cardiomyopathy. More than 250 publications were retrieved using these search criteria. Only four papers, all dealing with Case Reports, proved to be relevant for the present discussion. As shown in Table 1, a severe impairment of heart function was reported in only five patients (four women and one man) with Cushing’s syndrome, including our one. Echocardiographic findings in these patients showed that their mean EF was low at presentation, but it significantly improved after restoration of normal serum levels of cortisol (39 ± 16% vs 60 ± 6%, at presentation and after the cure of Cushing’s syndrome, respectively; Student t-test for paired data, P < 0Æ05). None of these patients had coronary artery involvement. The apparently normal EF of the patient described by Kamiya et al. was found at her 24th week of gestation, when a higher EF would be expected. Typical signs of Cushing’s syndrome were present in all previously described patients with one exception. The degree of serum cortisol elevation was highly variable, ranging from a 1Æ1to a 4Æ6-fold increase above the upper limit of the normal reference range. This observation is in agreement with previous studies, indicating that the duration of exposure to hypercortisolism rather than the absolute levels of circulating cortisol is the main determinant of left ventricular concentric remodelling. As in most cases of Cushing’s disease, the precise time at onset of the disease cannot be ascertained in our patient. However, our patient had been diagnosed with hypertension since 4 years and he had suffered an aseptic necrosis of the femoral head 6 years before.