Use of Methotrexate to Treat Isolated Graves Ophthalmopathy Developing Years After Thyroidectomy and Iodine 131 Treatment of Papillary Thyroid Cancer

ObjectiveTo describe a case of Graves ophthalmopathy developing years after subtotal thyroidectomy and radioactive iodine treatment of papillary thyroid cancer.MethodsWe present a case report including clinical and laboratory data. Current relevant literature is reviewed and summarized with regard to Graves ophthalmopathy.ResultsIn 2001, a 51-year-old woman presented with an asymptomatic thyroid nodule. Fine-needle aspiration biopsy results showed Hürthle cells, and the patient had a subtotal thyroidectomy in 2002. Stage 2 follicular variant of papillary thyroid carcinoma was diagnosed. She received radioactive iodine (I 131) therapy (94.8 mCi and 147.2 mCi) in 2003. Thyrotropin was suppressed with levothyroxine. The patient remained asymptomatic and had undetectable thyroglobulin antibodies. In 2007, her eyes became irritated (ie, erythematous, pruritic, watery). Thyroperoxidase and thyroglobulin antibodies were undetectable, but thyrotropin receptor antibody was elevated to 44% (reference range, < 16%). On physical examination, moderate periorbital edema and conjunctival injection were present; orbital magnetic resonance imaging was normal. Computed tomography of her orbits showed symmetric bilateral exophthalmos and prominence of orbital fat. Other ophthalmologic etiologies were ruled out by 2 independent ophthalmologists. She had minimal improvement with oral and intravenous steroids. Subsequent treatment with methotrexate resulted in marked symptomatic improvement and lowered the thyrotropin receptor antibody level to 24%.ConclusionsIsolated Graves ophthalmopathy in a patient after treatment of thyroid cancer and radioactive iodine ablation has not been previously reported. Methotrexate therapy may be a useful therapeutic approach in this setting. (Endocr Pract. 2008;14:422-425)     

Levothyroxine Replacement In Obese Hypothyroid Females After Total Thyroidectomy

Objective: Levothyroxine (LT4) replacement in hypothyroid obese patients is poorly understood. We assessed whether the LT4 regimen required to achieve euthyroidism differs between nonobese and obese hypothyroid females.Methods: We retrospectively identified nonobese and obese females who received LT4 starting with a standard dose of 1.6 μg/kg after total thyroidectomy for preoperative diagnosis of benign goiter. We examined the association between LT4 dosage required to achieve euthyroid state (thyroid-stimulating hormone [TSH] 0.4–2.5 mIU/L) and patient characteristics using linear regression models with and without adjustment for age, ethnicity, medication use, and postoperative hypoparathyroidism.Results: We identified 32 females (15 nonobese/17 obese) who achieved euthyroid state. Obese patients weighed more (104.1 ± 22.5 vs. 64.9 ± 10.0 kg, P<.0001) and required a higher final LT4 than nonobese (146 ± 38 vs. 102 ± 12 μg, P = .0002) but LT4 requirements per kg total body weight (TBW) were similar (1.60 ± 0.29 vs. 1.42 ± 0.38 μg/kg, P = .15). LT4 dose per kg ideal body weight (IBW) was higher in obese than in nonobese females (2.62 ± 0.67 vs. 1.88 ± 0.28 μg/kg, P = .0004) and this difference persisted after adjustments (P<.05). During LT4 titration, 47% and 20% of obese and nonobese patients had subnormal TSH episodes, respectively (P = .11). After taking LT4 compliance, malabsorption, and competing medication use into consideration, we found marked LT4 dose variability in obese patients. Patients who needed a mean daily LT4 dose ≤150 mg (124 ± 16 μg/day) compared with >150 μg (198 ± 4 μg/day) demonstrated lower LT4 per TBW (1.25 ± 0.18 vs. 1.84 ± 0.43 μg/kg, P = .03) and IBW (2.28 ± 0.47 vs. 3.44 ± 0.18 μg/kg, P<.0001), respectively.Conclusion: The standard approach to LT4 replacement in obese and nonobese females after thyroidectomy is imprecise. Mean daily LT4 doses in obese and nonobese patients were similar if expressed per kg TBW, though there was variability in the final LT4 among obese patients. We suggest initiating LT4 at a dose lower than that routinely recommended in obese females.Abbreviations:AACE = American Association of Clinical EndocrinologistsATA = American Thyroid AssociationBMI = body mass indexIBW = ideal body weightLT4 = levothyroxineTBW = total body weightTSH = thyroid-stimulating hormone     

Intrathyroidal Ectopic Thymic Tissue Mimicking Thyroid Cancer in Children

ObjectiveTo increase awareness of the important differential diagnosis between thyroid cancer and intrathyroidal ectopic thymic tissue when performing neck ultrasound (US) in pediatric patients.MethodsWe report 2 cases of intrathyrodal thymic tissue that were initially referred as possible papillary thyroid cancer (PTC). US and cytologic features of these lesions are described, and the distinguishing US characteristics of intrathyroidal thymic tissue versus PTC are discussed.ResultsTwo pediatric patients who underwent thyroid US were diagnosed with thyroid nodules suggestive of PTC. The suspected lesions in both patients exhibited an echo texture identical to the normal thymus gland. Fine-needle aspirate (FNA) biopsy of the nodule in the first case revealed numerous lymphocytes with positive immunocytochemical staining for CD3, confirming a T cell phenotype. The second patient underwent follow-up US imaging 8 months later that showed stability of the intrathyroidal nodule.ConclusionIntrathyroidal ectopic thymic tissue can be mistaken for PTC as both conditions have similar US features. Increased awareness of this unique mimicry may help to avoid unnecessary invasive investigations and surgery in these young patients. (Endocr Pract. 2014;20: e241-e245)     

Scintigraphic Detection of Dual Ectopic Thyroid Tissue: Experience of a Chinese Tertiary Hospital

Purpose

To assess scintigraphic pattern, clinical indication and relevance of dual ectopic thyroid tissue (ETT). Literature is reviewed for such cases.

Methods

In this 5-year retrospective study, we reviewed all thyroid scintigraphies in our data base. Patients diagnosed with suspected ETT were identified. Literature is reviewed. Statistics were done by one-way analysis of variance and least significant difference test.

Results

From 11905 thyroid scintigraphies during the 5-year period, we retrieved 121 patients eligible for analysis. The top two indications were assessing a palpable front neck mass to determine whether it was an ETT, and primary hypothyroidism. Patients were divided into 3 groups. Group 1 with single ETT (83 cases); group 2 with dual ETT (6 cases) and group 3 with athyroid (32 cases). Age and thyroid hormones were highest in group 2, and lowest in group 3. Thyrotropin was highest in group 3, and lowest in group 2. Thyroxine was given to hypothyroid patients, while no surgery was performed. There were 42 published cases with dual ETT, most of whom were under 30 years old. 38.10% of them were euthyroid, 33.33% hypothyroid, and 21.43% subclinical hypothyroid. Most frequent ectopic positions included lingual (33.73%), sublingual (27.71%) and subhyoid (22.89%).

Conclusions

In our cohort, incidence of dual ETT was 0.05% if the denominator was total number of thyroid scintigraphies. The incidence was 4.96% if the denominator was the number of patients with suspected ETT. Important clinical indication is a front neck palpable mass suggestive of an ETT. Important clinical relevance of recognizing the dual ETT pattern is to avoid inappropriate surgery. After reviewing all published cases, we find dual ETT is often seen in young patients. Most of such patients are euthyroid or mildly hypothyroid. Thyroid ectopia often resides in lingual, sublingual and subhyoid areas.     

Ectopic ACTH syndrome due to Grawitz tumor

An extremely unusual case of adrenocorticotropin (ACTH)-producing Grawitz tumor is reported in a 56-year-old female. The clinical feature of the patient was compatible with Cushing's syndrome. The plasma levels of ACTH and cortisol were markedly elevated. At autopsy, a left renal tumor was demonstrated and its histopathological diagnosis was renal cell carcinoma (Grawitz tumor). The adrenal gland was bilaterally enlarged with diffuse hyperplasia of the fasciculate zone. The adenohypophyseal cells were atrophic and showed Crooke's degeneration. The tumor contained extremely high levels of ACTH, beta-lipotropin and beta-endorphin. The presence of large molecular weight forms of ACTH has also been demonstrated by a Sephadex G-50 gel filtration of the tumor extract. We authors believe that this is the first documented case of ACTH-producing Grawitz tumor in the literature.     

The Optimal Parathyroid Hormone Cut-Off Threshold for Early and Safe Management of Hypocalcemia After Total Thyroidectomy

ObjectiveTo define optimal intact parathyroid hormone (iPTH) cut-off threshold predictive of hypocalcemia after total thyroidectomy for safe and effective postoperative management.MethodsThis prospective single center study was done in 2 phases. In phase I, predictors of symptomatic hypocalcemia were analyzed and the receiver operating characteristic curve was used to define the optimal iPTH cut-off threshold predictive of hypocalcemia. Phase II studied giving prompt prophylactic supplemental calcium and vitamin D to all patients who had iPTH levels below the calculated threshold, while phase I patients were given prompt selective supplementation if they had postoperative hypocalcemia or symptoms.ResultsUnivariate analysis of patients in phase I showed that postoperative iPTH was the only significant variable that can predict symptomatic hypocalcemia. Using receiver operating characteristic curve and Youden index, the confirmed optimal cut-off threshold predictive of hypocalcemia was iPTH 19.95 pg/mL, with area under the curve of 0.903, 100% sensitivity, negative predictive value, and highest Youden index, while iPTH 15 pg/mL and iPTH 10 pg/mL were less optimal. Symptomatic hypocalcemia occurred in 30% of the phase I cohort who received selective supplementation versus 3% of those in the phase II cohort who received prophylactic supplementation. Return to emergency department and need for intravenous calcium were also significantly better in phase II.ConclusioniPTH cut-off for post-thyroidectomy hypocalcemia was 19.95 pg/mL. Low-risk patients were discharged with no supplementation while all high-risk patients received prompt calcium and vitamin D supplementation, which led to effective hypocalcemia management and safe 24-hour discharge.     

甲状腺全切术治疗分化型甲状腺癌的疗效观察及临床研究探讨

目的:研究甲状腺全切术治疗分化型甲状腺癌的疗效观察及临床研究探讨。方法:收集2014年3月至2015年3月我院收治的90例分化型甲状腺癌患者,按抽签法分为实验组和对照组,每组45例。对照组采用次全切除术治疗,实验组采用甲状腺全切术治疗。观察两组患者的治疗疗效、手术时间、术中出血量、住院时间、复发率、治疗前后血清TNF-α、IL-6、Gal-3、VEGF水平及并发症的发生情况。结果:治疗后,实验组总有效率显著高于对照组[93.33%(42/45)vs68.89%(31/45)](P0.05)。两组住院时间比较差异无统计学意义(P0.05),实验组手术时间、术中出血量、复发率均显著低于对照组[(70.36±12.72)min vs(109.75±15.37)min,(50.28±10.64)mL vs(91.62±13.50)mL,2.22%(1/45)vs15.56%(7/45)](P0.05);治疗后血清TNF-α、IL-6、Gal-3、VEGF水平均显著低于对照组[(506.30±78.23)pg/mL vs(621.25±83.54)pg/mL,(73.29±10.32)pg/mL vs(102.58±12.49)pg/mL,(3.40±0.80)ng/mL vs(4.82±0.81)ng/mL,(16.21±4.02)pg/mL vs(20.75±5.23)pg/mL](P0.05)。实验组和对照组并发症总发生率分别为15.56%、6.66%,两组比较差异无统计学意义(P0.05)。结论:甲状腺全切术治疗分化型甲状腺癌的疗效优于次全切除术治疗,可彻底清除病灶,降低复发率,可能与有效降低患者血清TNF-α、IL-6、Gal-3、VEGF水平有关,但其并发症较多,对于低危或术后无需放射治疗的患者可采用次全切除术治疗,应慎重选择手术方式。     

甲状腺全切除术与双叶切除术对甲状腺微小癌患者血清甲状腺激素水平、预后及生活质量的影响

目的:探讨甲状腺全切除术与双叶切除术对甲状腺微小癌患者血清甲状腺激素水平、预后及生活质量的影响。方法:回顾性分析2016年2月～2018年8月期间我院收治的甲状腺微小癌患者103例的临床资料,根据手术方式的不同分为A组(n=50,双叶切除术)和B组(n=53,甲状腺全切除术),比较两组围术期指标、甲状腺激素水平、生活质量、并发症及复发情况。结果:B组术中出血量少于A组,手术时间、住院时间、切口长度短于A组(P0.05)。术后3个月,两组血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平均较术前降低,且B组低于A组(P0.05)。术后12个月,两组生活质量简表(SF-36)量表各维度评分均较术前升高,且B组高于A组(P0.05)。B组并发症发生率低于A组(P0.05);两组复发率比较差异无统计学意义(P0.05)。结论:甲状腺全切除术治疗甲状腺微小癌患者的预后与双叶切除术相当,可有效改善临床指标、生活质量和甲状腺功能,同时还可减少并发症发生率。     

Ultrasonographic Differentiation of Cervical Lymph Nodes in Patients with Papillary Thyroid Carcinoma After Thyroidectomy and Radioiodine Ablation: A Prospective Study

ObjectiveThe objective of the present study was to validate an ultrasound (US) classification of cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC) after thyroidectomy and radioactive iodine (¹³¹I) ablation.MethodsWe performed a prospective study in which the patients were submitted to thyroidectomy and ¹³¹I ablation and then followed until neck US revealed LN(s) ≥ 5 mm. A total of 288 LNs from 112 patients with PTC were evaluated. Patient management was based on LN characteristics grouped according to the classification system studied here.ResultsThe presence of microcalcifications and/or cystic degeneration of cervical LNs were highly suggestive of a metastatic etiology (specificity of 99.4%). In contrast, the most sensitive finding for LNs affected by PTC was the absence of an echogenic hilum (sensitivity of 100%). In the absence of these findings (microcalcifications, cystic degeneration, echogenic hilum), a metastatic etiology was the most likely in the case of a round LN (specificity of 89%). The differentiation of a spindle-shaped LN without a visible hilum by Doppler analysis permitted us to dichotomize an initial probability of metastases of 13% in 25% (with peripheral vascularization) versus 3.3% (without peripheral vascularization).ConclusionsOur results confirm that the classification proposed for cervical LNs in patients with PTC is valid for determining patient management following initial therapy. (Endocr Pract. 2014;20:293-298)     

Incidence,Risk Factors,and Clinical Implications of Delayed Hypoparathyroidism on Postoperative Day two Following Total Thyroidectomy for Papillary Thyroid Carcinoma

Objective: This study aimed to investigate the incidence rates, risk factors, and clinical implications of delayed hypoparathyroidism on postoperative day 2 (POD-2) after total thyroidectomy in patients with papillary thyroid carcinoma.Methods: This study included 410 patients with normal serum intact parathyroid hormone (iPTH) and calcium levels on postoperative day 1 (POD-1) who were classified into 2 groups according to the presence or absence of delayed hypoparathyroidism on POD-2.Results: Of the 410 patients, 98 experienced delayed hypoparathyroidism on POD-2 (23.9%). The significant risk factors for delayed hypoparathyroidism on POD-2 included female gender, age older than 45 years, central lymph node dissection, increased number of excised lymph nodes, and low POD-1 versus preoperative iPTH ratios. Additionally, delayed hypoparathyroidism on POD-2 was found to be a significant risk factor for hypocalcemia on POD-2 and permanent hypoparathyroidism.Conclusion: Prophylactic calcium supplementation and long-term surveillance for permanent hypoparathyroidism should be considered in patients with risk factors for delayed hypoparathyroidism on POD-2.Abbreviations: CI = confidence interval; iPTH = intact parathyroid hormone; OR = odds ratio; POD-1 = postoperative day 1; POD-2 = postoperative day 2; PTC = papillary thyroid carcinoma; ROC = receiver operating characteristic     

血清microRNA-335对根治术并碘131治疗的分化型甲状腺癌预后判断的临床价值分析

目的:探讨血清microRNA-335对根治术并碘131清甲治疗的分化型甲状腺癌预后判断的临床价值。方法:采用实时荧光定量PCR技术检测100例经甲状腺癌根治术(甲状腺癌全切+肿瘤同侧中央组淋巴结清扫术)并碘131清甲治疗后的分化型甲状腺癌患者血清中microRNA-335的相对表达量,并用Pearson相关性分析法来分析其与患者术后复发时间的相关性。结果:100例分化型甲状腺癌患者经根治术并碘131清甲治疗后2周后血清microRNA-335水平较治疗前明显降低(P0.0001)。15例复发的患血清microRNA-335水平较未复发患者显著升高(P0.05),且与其复发时间呈显著正相关(P0.0001)。结论:分化型甲状腺癌患者经甲状腺癌根治术并碘131清甲治疗后血清microRNA-335水平升高可能有助于预测其复发。     

Ectopic Acromegaly due to A Pancreatic Neuroendocrine Tumor Producing Growth Hormone-Releasing Hormone

ObjectiveTo present a case of acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion from a pancreatic neuroendocrine tumor in the context of multiple endocrine neoplasia type 1 (MEN 1).MethodsWe describe the clinical, imaging, and pathologic findings of the study patient.ResultsA 46 year old woman presented with clinical and biochemical findings diagnostic of acromegaly. Magnetic resonance imaging showed a 1.2-cm sellar mass. Following resection of the macroadenoma, serum insulinlike growth factor 1 (IGF-1) and growth hormone (GH) levels remained unchanged. Pathologic examination revealed adenomatous changes, including a nonsecretory focus and a prolactin immunopositive area (GH stain negative in both). Octreotide long-acting release was ineffective. Search for an ectopic tumor included normal octreoscan and abdominal computed tomography. GHRH was greater than 1000 pg/mL. Repeated abdominal computed tomography documented a 6.2-cm mass in the tail and body of the pancreas. Distal pancreatectomy revealed a pancreatic neuroendocrine tumor that stained positive for GHRH. Postoperatively, serum GHRH and IGF-1 normalized. Re-evaluation of the initial pituitary pathologic specimen revealed additional somatotroph hyperplasia of the adjacent, normal pituitary gland. Primary hyperparathyroidism was diagnosed, and multigland parathyroid hyperplasia was noted at surgery. Genetic testing was positive for a mutation in the MEN1 gene.ConclusionThis patient’s acromegaly was resistant to somatostatin analogue therapy, reflecting the negative octreoscan imaging. In addition, this case is novel because the patient presented with pituitary adenomatous changes, which were presumably associated with MEN 1 and/or possibly the elevated GHRH levels. (Endocr Pract. 2011; 17:79-84)     

Years of life lost due to Huntington disease.

Many genetic diseases shorten the lives of people who have them. Hence, it makes sense to speak of years of life lost due to cystic fibrosis or sickle-cell anemia or numerous other genetic disorders. In conventional practice, years of life lost is calculated for causes of death only, but a genetic disease is better understood as a risk-altering state or condition: it acts not at the time of death only but from birth onwards. Therefore, we must reformulate the concept of years of life lost before applying it to genetic conditions. This has already been done for congenital genetic diseases. This paper extends the reformulation to diseases with delayed onset. Huntington disease (HD) is used as an example.     

Tissue strains induced in airways due to mechanical ventilation

Better understanding of the stress/strain environment in airway tissues is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. Airway tissue strains responsible for stressing the lung's fiber network and rupturing the lung due to compliant airways are very difficult to measure experimentally. A computational model that incorporates the heterogeneity of the airways was developed to study the effects of airway tissue material properties on strain distributions within each layer of the airway wall. The geometry and boundary conditions of the tissue strain analysis were obtained from the organ-level analysis model. Two sets of airway tissue properties (heterogeneous and homogeneous) were considered in order to estimate the strain levels induced within the tissue. The simulation results showed that the homogeneous model overestimated the maximum strain in the mucosa layer and underestimated the maximum strain in the smooth muscle and cartilage layers. The results of strain levels obtained from the tissue analysis are very important because these strains at the cellular-level can create inflammatory responses, thus damaging the airway tissues.