Primary Thyroid Disease Research Articles

S2576 A Case Series of “Macro”-AST: A Clinical Entity Worth Recognizing Presidential Poster Award

INTRODUCTION: Aspartate aminotransferase (AST) is an enzyme found in both the mitochondria and cytosol of cells. An isolated elevation in AST may invoke a number of possible diagnoses, such as a primary muscle disease, celiac disease, thyroid disease and hemolytic disorders. The literature reports some cases of modest elevations in serum AST levels caused by the presence of a “macro”-AST, in which AST complexes with immunoglobulin (Ig). CASE DESCRIPTION/METHODS: Herein we describe 5 patients who presented to our university-based outpatient hepatology practice with an isolated elevation in serum AST levels. As can be seen from Table 1, the serum ALT was always within normal limits and the degree of peak AST elevation was variable (ranging from 3 to 10 times the upper limit of normal). In all cases, work-up for liver disease was negative, i.e. viral, autoimmune, genetic, fatty and drug-induced liver disease. Liver imaging was unremarkable and additional testing for skeletal muscle, thyroid, hemolytic disorders and celiac disease were all negative. One patient had undergone liver biopsy prior to referral, which was normal. In all 5 cases, the presence of “Macro”-AST was diagnosed by polyethylene glycol (PEG) precipitation technique (performed at the Mayo Clinic laboratories). DISCUSSION: “Macro”-AST is a high molecular weight form of AST that is usually formed through association with Ig in the circulation. As a result of reduced inactivation, clearance or excretion, AST values are persistently increased. This can lead to problems interpreting the values if clinicians are unfamiliar with this phenomenon. The pathogenesis of the enzyme elevation remains speculative, although an autoimmune process may be involved. Methods to detect the macromolecule may include PEG precipitation, ultrafiltration or electrophoresis. AST levels in “macro”-AST patients can fluctuate over time and may, in fact, be occasionally normal. The appreciation of this condition can obviate the need for more invasive investigations and it is important to recognize this laboratory phenomenon to reassure patients of its benign significance.Table 1.: Review of 5 Cases of “Macro”-AST

The Differential Diagnosis of Discrepant Thyroid Function Tests: Insistent Pitfalls and Updated Flow-Chart Based on a Long-Standing Experience.

Background: Discrepant thyroid function tests (TFTs) are typical of inappropriate secretion of TSH (IST), a rare entity encompassing TSH-secreting adenomas (TSHoma) and Resistance to Thyroid Hormone (RTHβ) due to THRB mutations. The differential diagnosis remains a clinical challenge in most of the cases. The objective of this study was to share our experience with patients presenting with discrepant TFTs outlining the main pitfalls in the differential diagnosis.Methods: medical records of 100 subjects with discrepant TFTs referred to Thyroid Endocrine Centers at the University of Milan were analyzed, retrospectively. Patients were studied by dynamic testing (TRH test, T3-suppression test, or a short course of long-acting somatostatin analog, when appropriate), THRB sequencing, and pituitary imaging.Results: 88 patients were correctly diagnosed as RTHβ with (n = 59; 16 men, 43 women) or without THRB variants (n = 6; 2 men, 4 female) or TSHoma (n = 23; 9 men, 14 women). We identified 14 representative subjects with an atypical presentation or who were misdiagnosed. Seven patients, with spurious hyperthyroxinemia due to assays interference were erroneously classified as RTHβ (n = 4) or TSHoma (n = 3). Three patients with genuine TSHomas were classified as laboratory artifact (n = 2) or RTHβ (n = 1). Two TSHomas presented atypically due to coexistent primary thyroid diseases. In one RTHβ a drug-induced thyroid dysfunction was primarily assumed. These patients experienced a mean diagnostic delay of 26 ± 14 months. Analysis of the investigations which can differentiate between TSHoma and RTHβ showed highest accuracy for the T3-suppression test (100% specificity with a cut-off of TSH <0.11 μUI/ml). Pituitary MRI was negative in 6/26 TSHomas, while 11/45 RTHβ patients had small pituitary lesions, leading to unnecessary surgery in one case.Conclusions: Diagnostic delay and inappropriate treatments still occur in too many cases with discrepant TFTs suggestive of central hyperthyroidism. The insistent pitfalls lead to a significant waste of resources. We propose a revised flow-chart for the differential diagnosis.

Central hypothyroidism or subclinical hyperthyroidism: can they be confused with each other?

SummaryIsolated, adult-onset central hypothyroidism is very rare, and its diagnosis can be challenging. A 42-year-old patient was referred for evaluation of a 2.8 cm thyroid nodule. She referred symptoms that could be attributed to hypothyroidism and thyroid tests showed low TSH and normal-low levels of free T4. However, evaluation of the remaining pituitary hormones and pituitary MRI were normal, yet a radionuclide scanning revealed that the thyroid nodule was ‘hot’ and the tracer uptake in the remaining thyroid tissue was suppressed. Interpretation of these studies led to a misdiagnosis of subclinical hyperthyroidism and the patient was treated with radioiodine. Soon after treatment, she developed a frank hypothyroidism without appropriate elevation of TSH and the diagnosis of central hypothyroidism was made a posteriori. Long term follow-up revealed a progressive pituitary failure, with subsequent deficiency of ACTH and GH. This case should alert to the possibility of overlooking central hypothyroidism in patients simultaneously bearing primary thyroid diseases able to cause subclinical hyperthyroidism.Learning points:Although rarely, acquired central hypothyroidism can occur in the absence of other pituitary hormone deficiencies.In these cases, diagnosis is challenging, as symptoms are unspecific and usually mild, and laboratory findings are variable, including low, normal or even slightly elevated TSH levels, along with low or low-normal concentrations of free T4.In cases with low TSH levels, the coexistence of otherwise common disorders able to cause primary thyroid hyperfunction, such as autonomous nodular disease, may lead to a misdiagnosis of subclinical hyperthyroidism.

Primary Thyroid Lymphoma in an Adolescent with Hashimoto’s Thyroiditis and Congenital Deafness

Background: Primary thyroid lymphoma is extremely rare in children and adolescents. The diagnosis of thyroid malignancies is often made secondary to other thyroid pathologies including Hashimoto’s thyroiditis (HT). Case Presentation: This case describes a 14-year-old girl with a background of HT and congenital deafness that presented with a rapidly enlarging multinodular thyroid mass. She underwent a total thyroidectomy and a diffuse, large B-cell lymphoma was diagnosed on pathology. Discussion: Primary thyroid disease is an extremely rare disease in childhood, usually presenting as a rapidly enlarging goitre. The correlation between Hashimoto’s thyroiditis and primary thyroid lymphoma is well-established in adults but has not been verified in the paediatric population. Our patient also has βthalassemia and Usher syndrome, however, no correlation between these and primary thyroid lymphoma could be found in the literature. Conclusion: It is important to include malignancy in the differential diagnosis of thyroid enlargement or unexplained symptoms, especially in the presence of syndromes. Further research into the relation between lymphomas and HT in the paediatric population is needed.

OR18-05 Thyroid Hormone Use and Survival among Older Adults - Longitudinal Analysis of the Baltimore Longitudinal Study of Aging (BLSA)

: Introduction: Thyrotropin (TSH) levels on average are higher and vary more widely among older adults.1 Large meta-analyses and treatment trials for isolated elevated TSH in older adults did not demonstrate harm from no treatment or benefit from treatment in this population.2 Isolated, elevated TSH can result from adaptations to aging, rather than primary thyroid disease, suggesting that thyroid hormone treatment could actually cause harm.3 Objective:To determine if there is a survival effect from thyroid hormone treatment in adults aged 65+. Methodology:Thyroid functional status and thyroid hormone exposure were analyzed for 1,258 participants of the BLSA aged 65+ through death or end of follow up. We analyzed exposures by visit and also compared survival between individuals with consistently elevated, euthyroid or low TSH both on and off of therapy.Incident rate ratios (IRR) were calculated using time-dependent Poisson regression models. Covariates included age, sex, race, walking index (measure of physical function), self-rated health (SF-12), body mass index (BMI), smoking and comorbidity score. Results: Average follow-up was 9 years, with 169 deaths over the study period. The cohort comprised 49.5% women, with average age in the study being 78 years (SD ±8.2). Thyroid hormone use trended towards harm analyzed at each visit with an IRR=1.40 (95% CI 0.93–2.12) after adjusting for other covariates. Among ‘treated-to-target’versus euthyroid individuals, thyroid hormone use was associated with a significantly increased mortality rate with an IRR=1.80 (95% CI 1.09–2.96) in multivariable analysis. Conclusion: Thyroid hormone replacement among older adults,even when treated-to-target, is associated with a significantly increased mortality risk compared to euthyroid individuals with no history of thyroid hormone exposure. This suggests that treating isolated elevated TSH when changes are aging adaptations rather than primary thyroid disease could adversely affect health by altering key homeostatic adaptation. We recommend clinicians consider the underlying physiology of aging and employ age specific reference ranges when deciding on treatment for elevated TSH in older adults.4

SUN-298 Spectrum of Imaging in Immune Checkpoint Inhibitor Induced Hypophysitis

Background: Hypophysitis (HP) is a known immune related adverse event of immune checkpoint inhibitors (CPIs), commonly associated with CTLA-4 inhibitors and rarely with PD-1/PD-L1 inhibitors. Prior studies of MRIs at HP diagnosis noted pituitary enlargement with resolution within a few weeks. In this study, we examine MRI changes in patients with CPI-induced HP. Methods: Subjects with biochemical evidence of central hypothyroidism or central adrenal insufficiency and MRIs were reviewed by endocrinology and neuroradiology. MRIs were classified relative to HP diagnosis: baseline (at least 21 days prior), diagnosis (within 21 days), and follow up (over 21 days). Patient characteristics included age at CPI initiation, sex, race/ethnicity, personal and family history of autoimmunity, type of cancer and CPI. Results: Twenty-six subjects met the inclusion criteria. The mean age was 59 years; 62% were male and 86% were non-Hispanic white. Nineteen percent had a personal history and 31% a family history of autoimmunity. Fifty percent had melanoma. At HP diagnosis, 46% were on PD-1/PD-L1 inhibitors, 42% were on combination PD-1/CTLA-4 inhibitors and 12% were on CTLA-4 inhibitors.Median time from CPI initiation to HP diagnosis was 95 days. Time to HP was shorter on a CTLA-4 inhibitor combination or monotherapy (median 82 days) compared to a PD-1/PD-L1 inhibitor monotherapy (median 220 days; Wilcoxon rank sum, p <0.01). Central adrenal insufficiency was present in all patients not yet on steroids. Central hypothyroidism was common (10/19) in those without primary thyroid disease and was not associated with type of CPI (Fisher’s exact, p=0.18).Thirteen subjects had baseline MRIs, 18 had MRIs at HP diagnosis and 13 had MRIs in the follow up period. Baseline MRIs were normal in 12/13; one subject had an enlarged pituitary. At diagnosis, 10 had an enlarged pituitary, 7 a normal pituitary and 1 a partially empty sella. CTLA-4 inhibitor exposure was associated with pituitary enlargement at diagnosis: 9/11 compared to 1/7 on PD-1/PD-L1 inhibitor (Fisher’s exact, p <0.04). Of the subjects who had follow-up MRIs, 3 had an enlarged pituitary, 7 a normal pituitary and 3 a partially empty sella. Follow up imaging did not differ between treatment types (Fisher’s exact, p >0.05). Timing of MRI was significantly associated with pituitary appearance (Fisher’s exact, p <0.01). Conclusion: The MRI appearance of HP presents as a spectrum, from a partially empty sella, normal pituitary to an enlarged pituitary. HP diagnosed in the setting of CTLA-4 inhibitor treatment occurs earlier and is more likely to induce an enlarged pituitary gland compared to PD-1/PD-L1 monotherapy, which occurs later and is associated with a normal appearing MRI at diagnosis. This suggests that the pathogenesis of HP following CPI exposure may vary depending on the type of CPI.

MON-246 A Diagnostic Dilemma of Primary Versus Secondary Thyroid and Adrenal Hormone Insufficiencies: A Unique Case of Widely Metastatic Renal Cell Carcinoma After Brain Radiation

Background Identifying the etiology of hormonal insufficiency is important for correct diagnosis and for appropriate hormone supplementation. Usually multiple hormone deficiencies are driven by pituitary pathology, but here we present a case that poses a unique diagnostic and therapeutic dilemma. Clinical Case A 55 y/o lady with HTN and recently diagnosed metastatic Renal Cell Carcinoma (RCC) presented with weakness, dizziness, altered mental status, polydipsia and polyuria. Her metastases included the bilateral adrenal glands, thyroid, brain, and she had a sellar lesion displacing the pituitary as well as infundibular thickening. She had been treated with dexamethasone due to vasogenic edema, whole brain radiation, and was going to start immunotherapy (Ipilumimab&Nivolumimab). On exam she had relative hypotension and tachycardia (BP 115/58, HR 108). She was diagnosed with non-PTH mediated hypercalcemia (Ca 13.9/ 15.3 corrected for albumin 2.3, PTH 6.5, PTH-RP 69, Vitamin D-25 19.4). Her calcium normalized after fluid resuscitation and bisphosphonate treatment, but weakness and hypotension persisted. We tested thyroid and adrenal function given the location of her lesions, recent whole brain radiation, and recent steroid use. Her TSH was 0.017 (0.270 - 4.200 µIU/mL), fT4 0.84 (0.80 - 1.50 ng/dL), T3 0.59 (72.0 - 153.0 ng/dL), ACTH was 1.7 (7.2-63.3 pg/ml), cortisol 1.3 (6.0 - 18.4 ug/dL), aldosterone 3 (< or = 28 ng/dL), renin 7.87 (0.25 - 5.82 ng/mL/h), renin/aldosterone 0.4 (0.9 - 28.9). At 30 minutes after cosyntropin administration cortisol was 7.7 ug/dL, aldosterone 26 ng/dL, and at 60 minutes cortisol was 10.3 ug/dL. Hydrocortisone was initiated while tapering off dexamethasone, and levothyroxine was offered but declined. She opted to postpone further workup. Conclusion This patient presents a dilemma in identifying the primary causes of hormonal abnormalities given potential pituitary and primary thyroid and adrenal disease. The thyroid abnormalities could represent sick euthyroid physiology with lower T4 to T3 conversion or the effects of steroids which can also suppress TSH vs. hypothalamic or pituitary disease. Primary hypothyroidism from gland destruction was unlikely. The low ACTH and cortisol levels were expected since she was on dexamethasone, but low aldosterone with raised renin activity was concerning for primary adrenal insufficiency. However, after cosyntropin the suboptimal cortisol yet preserved aldosterone response supported secondary or tertiary adrenal insufficiency, and only cortisol was supplemented. Understanding her endocrine disease had implications for longer term management given that replacement may only need to be temporary and adrenal recovery might be possible. Further, the use of a 30 minute aldosterone level can be helpful in cases where multiple factors and discrepant laboratory findings may exist.

Surgical Approach to Primary Hyperparathyroidism in Patients with Concomitant Thyroid Diseases: A Retrospective Single Center Study.

Background Primary hyperparathyroidism (PHPT) and thyroid diseases are a frequent concomitant occurrence, but the surgical approach to associated disease is still debated. Methods We retrospectively evaluated a series of PHPT patients focusing on thyroid disease and surgery. Results Among 238 PHPT patients undergoing parathyroidectomy (PTX) between 2002 and 2017, 128 were affected also by a benign thyroid disease, namely, goiter in 118 (76 multinodular (MNG) and 42 uninodular (UNG)), autoimmune thyroiditis in 10, and hyperthyroidism in 21. Surgical approach was unilateral neck exploration (UNE) in 59 patients and bilateral neck exploration (BNE) in 69. The PHPT cure rate was 94%. On comparing patients submitted to PTX only and PTX plus thyroidectomy (TX), in the latter MNG and hyperthyroidism were more frequent, and surgical time and length of stay were longer. No difference in surgical complications was found between patients undergoing UNE and BNE. Conclusion PHPT patients with a concomitant thyroid disease underwent double surgery in almost two-thirds of the cases, mostly by BNE. The main factors driving the decision to perform concomitant PTX and TX were the presence of thyroid nodular disease with the nodule site ipsilateral to the presurgically localized parathyroid adenoma.

Congenital Heart Disease and Thyroid Dysfunction: Combination, Association, and Implication.

Patients with congenital heart disease have higher prevalence of thyroid dysfunction due to embryonic and genetic coexistence. Marked changes in cardiac function occur secondary to alternations in thyroid hormone levels. Cardiac catheterizations or cardiac surgeries with cardiopulmonary bypass can cause abnormalities in the circulating hormones, in the absence of primary thyroid disease. Therefore, monitoring of thyroid function should be routinely performed in children with congenital heart disease. Thyroid hormone supplementation has been postulated as a possible therapeutic option; however, the therapeutic decisions should be made based on individual circumstances, symptoms, and the severity of the thyroid dysfunction. To describe the correlation between congenital heart disease in children and thyroid dysfunction and the debate on monitoring, intervention, and treatment. PubMed, Clinical Key, and the Cochrane Library were searched using keywords relevant to congenital heart disease/surgery, cardiopulmonary bypass, thyroid hormones, sick euthyroid syndrome, and cardiac catheterization. Studies were limited to the English language and to children 0 to 18 years old. Studies in adults with important findings were reviewed as well. All clinical studies believed to have relevance were considered. All relevant studies were reviewed, and the most pertinent data were incorporated in this review. There is lack of significant evidence concerning treatment for thyroid dysfunction in children with a congenital cardiac diagnosis. Adequately powered studies are needed before a uniform recommendation about treatment can be made.

Discordant findings on preoperative imaging for primary hyperparathyroidism and thyroid disease: Choosing the path to follow

BackgroundPreoperative localization of abnormal parathyroid glands in primary hyperparathyroidism is often obtained by sestamibi, and ultrasonography. We aimed to identify which modality is most accurate when laterality of abnormal glands on preoperative imaging is discordant. MethodsA single institution retrospective review identified 112 consecutive patients with primary hyperparathyroidism who underwent successful parathyroidectomy and sestamibi with pertechnetate. ResultsSestamibi with pertechnetate had a sensitivity of 72% and positive predictive value of 90%; ultrasonography had sensitivity of 50% and positive predictive value 80%. Patients with thyroiditis had lesser sensitivity and positive predictive value on sestamibi with pertechnetate (53% and 77%, respectively), in contrast to ultrasonography (54%, 88%, respectively). The sensitivity and positive predictive value of sestamibi with pertechnetate and ultrasonography did not differ in patients with thyroid nodules. Seventeen patients (15%) had discordant laterality on preoperative imaging. In discordant cases, sestamibi with pertechnetate was correct in 53% overall but in only 17% of those with thyroiditis (P = .01), whereas ultrasonography was correct in 26% overall but in 50% of those with thyroiditis (P = .01). ConclusionThyroiditis decreased the sensitivity and positive predictive value of sestamibi with pertechnetate in primary hyperparathyroidism. In patients with discordant laterality on preoperative imaging, sestamibi with pertechnetate is the more accurate choice to guide operative planning, although ultrasonography may be a better guide in those with thyroiditis.

SUN-600 Metastatic Clear Cell Renal Cell Carcinoma Involving the Thyroid Presenting as Dysphagia

Introduction Metastases to the thyroid represent 1.4-3% of all malignancies. We report a case of renal cell clear cell carcinoma with metastases involving the thyroid 5 years after left nephrectomy. 35 to 80% of patients with thyroid involvement present with multiorgan metastases. Overall prognosis for these patients is dismal, but thyroid metastasectomy for selected patients may offer good survival rates (30–50%). Clinical case 64-year-old Caucasian female was diagnosed with clear cell renal cell cancer (RCC) in 2012 and underwent left radical nephrectomy. A thyroid nodule was first noted in 2012 on her initial staging scans. This nodule, over time, increased in size. In June 2015, CT scan showed a 2.5 x 1.4 cm right thyroid mass which underwent FNA. The cytology was benign. In April 2017, she developed dysphagia. A CT of the neck revealed increase in size of the heterogeneously enhancing mass arising from the right lobe of the thyroid to 4.7 x 3.9 cm. Thyroid function tests were normal through these years. She underwent isthmusectomy and right subtotal thyroidectomy in July 2017. Final histopathology showed metastatic clear cell renal cell carcinoma (Tumor size: around 4 cm). TTF-1 (thyroid transcription factor 1) immunostain highlighted the thyroid follicular cells while RCC immunostain was focal positive in both tumor cells and follicular cells. Subsequent CT neck showed no evidence of disease progression in the neck. There were no enlarged, enhancing, or necrotic cervical lymph nodes. CT thorax/abdomen/pelvis demonstrated bilateral subcm pulmonary nodules, left adrenal nodule and pancreatic head mass. She was then started on pazopanib 800 mg in August 2017. She is currently on levothyroxine 75 mcg daily and most recent TSH was 3.20 µIU/mL (ref. range 0.45 - 5.33) and free T4 0.98 ng/dL (ref. range 0.70 - 1.70). Conclusion Metastases to the thyroid gland are rare in the clinical setting, with the most common primary tumor to metastasize to the thyroid being RCC. Approximately 20% of these patients have distant metastases at the time of diagnosis and 30% will develop metastases during follow-up. In autopsy series, the most common primary tumor to metastasize to thyroid is lung cancer. Presenting symptoms of thyroid metastasis are mostly similar to those with primary thyroid disease. Changes in thyroid function happen late and are uncommon. Regardless of time elapsed since the initial diagnosis of the primary neoplasm, disease recurrence or metastasis must be in the differential when patients present with new signs/symptoms. Although distant metastases carry an adverse prognosis, thyroid metastases have a better outcome than those elsewhere. In contradistinction to primary thyroid malignancy, metastasis to the thyroid is not sensitive to radioactive iodine. Majority will be treated with palliative intent; but for selected patients, lobectomy or total thyroidectomy may be performed.

A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors.

Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6% (95% CI, 3.9-8.1), which was higher than nivolumab (0.5%; 95% CI, 0.2-1.2) and pembrolizumab (1.1%; 95% CI, 0.5-2.6). PD-1/PD-L1 inhibitors had a higher incidence of thyroid dysfunction - particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4-9.8; pembrolizumab, 8.5%; 95% CI, 7.5-9.7; PD-L1, 5.5%; 95% CI, 4.4-6.8; ipilimumab, 3.8%; 95% CI, 2.6-5.5). Combination therapy was associated with a high incidence of hypothyroidism (10.2-16.4%), hyperthyroidism (9.4-10.4%), hypophysitis (8.8-10.5%), and primary adrenal insufficiency (5.2-7.6%). Diabetes mellitus and primary adrenal insufficiency were less frequent findings on monotherapy. Our meta-analysis shows a high incidence of endocrine adverse events provoked by single agent checkpoint blockade, further reinforced by combined treatment.

Unknown and Already Known Thyroid Abnormalities in Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) and thyroid diseases are highly prevalent in the general population, but the putative link between the 2 conditions remains unclear. A monocentric consecutive series of 434 patients with PHPT was retrospectively evaluated by lab and ultrasonography to look for thyroid abnormalities. Patients were classified in 3 groups: without thyroid abnormalities (group 1, n = 171), with thyroid diseases not previously known (group 2a, n = 69), and thyroid diseases previously known (group 2b, n = 194). In terms of thyroid disease, no significant difference was found between groups 2a and 2b, except for the significantly larger number of patients with toxic nodular goiter in group 2b. PHPT was more frequently symptomatic in group 2a than in group 2b, despite no differences in serum calcium, creatinine, parathyroid hormone (PTH), or 25-hydroxyvitamin D (25OHD) levels. A total of 60% of PHPT patients had a thyroid disease that was unknown prior to PHPT diagnosis in almost one-third of cases. The newly diagnosed and previously known thyroid diseases were similar, both mostly affecting postmenopausal females. Ab = antibody; aPHPT = asymptomatic PHPT; 25OHD = 25-hydroxyvitamin D; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; Tg = thyroglobulin; TPO = thyroperoxidase; TSH = thyroid-stimulating hormone; US = ultrasound.

Low triiodothyronine is associated with elevation of N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in dialysis patients

BackgroundLow thyroid hormone (TH) levels and myocardial damage are common in dialysis patients and are associated with mortality. However, little is known about the role of THs on myocardial damage as has been described in primary thyroid diseases. The aim of this study was to explore the potential relationship between low total triiodothyronine (total T3) and biomarkers of myocardial damage and the effect of their interaction on mortality, to ascertain if cardiovascular damage is the link between low THs and the risk of death in dialysis patients with CKD. Material and methodsTH plasma levels, nutritional markers, inflammation and myocardial damage were studied in 296 patients undergoing peritoneal dialysis or haemodialysis, who were followed up for 16 months to ascertain the association between biochemical variables and mortality. ResultsLow total T3 levels were found in 45% of patients, which was inversely correlated with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality. ConclusionsLow total T3 levels are common in dialysis patients and are associated with inflammation, malnutrition and myocardial damage. The latter may be the link between low THs and all-cause and cardiovascular mortality.

Adrenal Crisis and Autoimmune Polyglandular Syndromes

We report a 67-year-old woman who presented with adrenal crisis as a manifestation of autoimmune polyglandular syndrome 2, a polygenic disorder characterized by concurrent primary adrenal insufficiency and either autoimmune thyroid disease or type 1 diabetes mellitus.

La disminución de triyodotironina se asocia con la elevación del péptido natriurético cerebral N-terminal y con la mortalidad en pacientes en diálisis

BackgroundLow thyroid hormone (TH) levels and myocardial damage are common in dialysis patients and are associated with mortality. However, little is known about the role of THs on myocardial damage as has been described in primary thyroid diseases. The aim of this study was to explore the potential relationship between low total triiodothyronine (total T3) and biomarkers of myocardial damage and the effect of their interaction on mortality, to ascertain if cardiovascular damage is the link between low THs and the risk of death in dialysis patients with CKD. Material and methodsTH plasma levels, nutritional markers, inflammation and myocardial damage were studied in 296 patients undergoing peritoneal dialysis or haemodialysis, who were followed up for 16 months to ascertain the association between biochemical variables and mortality. ResultsLow total T3 levels were found in 45% of patients, which was inversely correlated with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality. ConclusionsLow total T3 levels are common in dialysis patients and are associated with inflammation, malnutrition and myocardial damage. The latter may be the link between low THs and all-cause and cardiovascular mortality.

Equivocal preoperative imaging including 18F-fluorocholine PET-CT in primary hyperparathyroidism and nodular thyroid disease - case report

Equivocal preoperative imaging including 18F-fluorocholine PET-CT in primary hyperparathyroidism and nodular thyroid disease - case report

Impact of free thyroxine levels and other clinical factors on bare metal stent restenosis.

Thyroid hormones have both direct and indirect effects on thermogenesis such as modulating vascular smooth muscle cell proliferation. However, the influence of more subtle changes in thyroid hormones on coronary atherosclerosis remains a matter of speculation. Smooth muscle cells play a crucial role in the pathogenesis of in-stent restenosis (ISR). However, the relationship between free thyroxine (fT4) and ISR has not been studied. In the present study, we aimed to assess the role of preprocedural serum fT4 level on the development of ISR in patients undergoing coronary bare metal stent (BMS) implantation. We enrolled and analyzed clinical, biochemical, and angiographic data from 705 consecutive patients without a history of primary thyroid disease [mean age 60.3 ± 9.3 years, 505 (72%) male]; all patients had undergone BMS implantation and further control coronary angiography owing to stable or unstable angina pectoris. Patients were divided into 3 tertiles based on preprocedural serum fT4 levels. ISR was observed in 53 (23%) patients in the lowest tertile, 82 (35%) patients in the second tertile, and 107 (46%) patients in the highest fT4 tertile (p < 0.001). Using multiple logistic regression analysis, five characteristics emerged as independent predictors of ISR: diabetes mellitus, smoking, HDL-cholesterol, stent length, and preprocedural serum fT4 level. In receiver operating characteristics curve analysis, fT4 level > 1.23 mg/dL had 70% sensitivity and 73% specificity (AUC: 0.75, p < 0.001) in predicting ISR. Higher preprocedural serum fT4 is a powerful and independent predictor of BMS restenosis in patients with stable and unstable angina pectoris.

Thyroid hormone supplementation following open-heart surgery in children

In patients undergoing open-heart surgery, abnormalities in thyroid hormone levels have been observed even in the absence of primary thyroid disease. These abnormal changes in thyroid hormone level and function have been found to be sufficient to affect myocardial performance and postoperative recovery. In the intensive care unit, postoperatively, it has been found that features such as low cardiac output, left ventricular dysfunction and prolonged ventilator support were associated with hypothyroidism. We reviewed the available literature on the effect of thyroid hormone supplementation in paediatric patients undergoing open-heart surgery under cardiopulmonary bypass and concluded that children after complex congenital cardiac surgery are at risk of developing a clinically significant hypothyroid state in the early postoperative period. In the literature where the effects of supplementation of thyroxine were studied, beneficial effects were observed in terms of reduced mechanical ventilation time, reduced inotropic support and intensive care unit stay, rapid achievement of negative fluid balance and early recovery. Supplementation with thyroid hormones enables a smoother postoperative recovery and is beneficial. The total duration of this therapy is, however, unclear.

Association of Thyroid Function with Severity of Coronary Artery Disease in Euthyroid Patients.

Thyroid hormone exerts multiple effects on the heart and vascular system. Variations of free T3 have been linked to coronary artery disease. We conducted a study to observe whether there is a relationship between the variation of the serum thyroid hormone levels (TSH, FT3 and FT4) and the presence and severity of CAD in the euthyroid patients. To study association of serum TSH, FT4 and FT3 levels within the normal range with presence and severity of coronary artery disease. A total of 100 euthyroid patients with stable angina, who underwent coronary angiography were enrolled in the study. Coronary artery disease was defined as >50% stenosis in the luminal diameter in at least one major epicardial coronary artery. The Gensini scoring system was used to define the severity of the CAD and serum TSH, FT3 and FT4 levels were measured by the chemiluminescence method. Single vessel disease was found in 23%, double vessel disease in 15% and triple vessel disease in 17% of patients. TSH and FT4 levels were also comparable between the groups. Normal coronary group had significantly higher mean FT3 values than triple vessel disease (p=0.004) and FT3 levels showed an inverse relation with Gensini score (Pearson's correlation =- 0.30) (p =0.002). A level of FT3 ≤ 2.7 predicted the severity of CAD with a 70% sensitivity and 60% specificity (area under curve (AUC): 0.755, p=0.001). In the absence of primary thyroid disease and acute coronary syndrome, the occurrence of CAD is associated with lower serum levels of FT3. FT3 and not the FT4 and TSH levels may be used as an indicator of increased risk for severe CAD. The present study clearly shows the existence of a strong association between the reduction of biologically active T3 and severity of coronary artery disease. However, low T3 state could be at first interpreted as just a biological risk factor of severe coronary artery disease; only the demonstration of beneficial effects on cardiovascular, end points of long term T3 replacement in CAD patients with low T3 state can answer this fundamental issue.