Does Marine Lenhart Syndrome really exist?

Primary hyperthyroidism is the result of overproduction of thyroid hormone resulting in the classic symptoms of tachycardia, weight loss, diaphoresis, and hyperdefecation. There are multiple common causes to include Graves’ disease, toxic multinodular goiter, and solitary toxic adenomas. Marine Lenhart Syndrome (MLS) is a rare cause of hyperthyroidism, caused by a coexistence of constitutively active thyroid nodules and Graves’ disease. In the original document of Marine and Lenhart, there is no distinction made between the autoimmune phenomenon of Graves’ disease and the solitary toxic nodule of Plummer’s disease. Rather they are both considered to be the manifestation of the same disease. However, in the current era of radionuclide technology, a clear distinction of MLS can be seen with diffuse uptake in the thyroid gland and focused enhancement in the toxic nodules. Therefore what was previously described as one entity is now distinct as Graves’ disease and Plummer’s disease. It is also becoming increasingly clear within the literature that there is also a new phenomenon of post-radioiodine immunogenic hyperthyroidism in patients with toxic nodules and elevated autoantibodies. Therefore in order to properly treat and manage patients, a new definition of MLS may need to be proposed.

PTH after Thyroidectomy as a Predictor of Post-Operative Hypocalcemia

Post-thyroidectomy hypocalcemia is a frequent complication with significant morbidity, and has been shown to increase hospital stay and readmission rates. The evaluation of serum parathyroid hormone (PTH) levels after thyroidectomy represents a reliable method to predict post-thyroidectomy hypocalcemia, but it remains infrequently used. This retrospective study investigates serum PTH values 3 h after thyroidectomy as a predictor of hypocalcemia. In this study, we enrolled 141 patients aged between 27 and 71 years eligible for total thyroidectomy who presented with multinodular goiter, suspicious nodule on cytological examination, Graves’ disease, or toxic multinodular goiter. Three hours after total thyroidectomy, 53 patients (37.6%) showed a reduction in serum PTH. Of these patients 75.5% developed hypocalcemia by 24 h after surgery and 100% were hypocalcemic after 48 h (p < 0.001). There was no significant difference attributable to the different thyroid diseases, nor to the age of the patients. PTH at 3 h after total thyroidectomy accurately predicts post-operative hypocalcemia. The early detection of patients at risk of developing post-operative hypocalcemia allows for prompt supplementation of calcium and Vitamin D in order to prevent symptoms and allows for a safe and timely discharge.

A higher cut-off for Thyroid-stimulating immunoglobulin (TSI) could better predict relapse in Graves’ disease?

Background: TSH receptor (TSHr)-stimulating immunoglobulins (Igs) can be used as diagnostic markers of Graves’ disease (GD). Thyroid-stimulating immunoglobulin (TSI) assays exclusively detect these specific Igs. Materials and Methods: This was a prospective longitudinal study in which hyperthyroid patients with GD and toxic nodular goitres were evaluated at diagnosis. GD patients were also evaluated at antithyroid drug (ATD) withdrawal. An automated chemiluminescent assay measured TSI. According to the manufacturer TSI less than 0.55 IU/L was a non-reactive result. The authors evaluated the Se and Sp of the cutoff point provided by the TSI assay manufacturer, and tested other cutting points through a ROC curve, to assess relapse risk of Graves’ disease. Results: At diagnosis, were evaluated 92 (85.2%) GD patients aged 41.2 ± 2.0 years, and 16 patients (14.8%) with toxic multinodular goiter (TMNG) or toxic adenoma (TA), aged 60.8 ± 4.8 years. They were re-evaluated after 18 ± 4 months with methimazole (MMI) treatment. The follow-up after treatment suspension was of 20 ± 6 months. At diagnosis, the TSI (Se) and (Sp) were 98.9% and 100%, respectively. At ATD withdrawal, despite a high Se (95.5%), Sp was low (59.6%). By adjusting the cut-off to 1.11 (TSI <1.11 IU/L non-reactive), TSI presented the best Sp (89.4%) with a small decrease in Se (93.3%) in predicting GD relapse. Conclusions: TSI had high Se and Sp in GD differential diagnosis with nodular goiters. In the assessment for GD relapse, by raising the cutting point to 1.11 IU/L, a better Sp was obtained at the expense of a small drop in Se. A larger sample is needed to support a higher TSI cut-off point in the clinical routine to assess GD relapse after ATD.

A Patient With Graves’ Disease And Thyroid-Associated Orbitopathy Undergoing Radioactive Iodine in Dr. Soetomo General Academic Hospital, Surabaya

Graves’ Disease (GD) is the most common etiology of thyrotoxicosis, followed by toxic multinodular goiter and toxic adenoma. GD can be managed with anti-thyroid drugs (ATDs), surgery, or radioactive iodine (RAI). Thyroid-associated orbitopathy (TAO) or Graves’ Ophthalmopathy (GO) affects 25%-50% patients with GD, and its presence usually dissuade clinicians to use RAI in treating hyperthyroidism. The presence of GO is a relative contraindication use of RAI in patients with GD, as RAI can worsen existing GO. Corticosteroid prophylaxis can be given to such patients to reduce likelihood of worsening of GO. However, patient with moderate to severe active GO is currently advised against undergoing RAI. Established guidelines recommend the use of corticosteroid prophylaxis in these patients. We reported a patients with GD and orbitopathy who was treated with RAI and was given steroid prophylaxis to prevent worsening of GO.

Study of the risk factors for post-operative hypocalcemia after thyroid surgery

Background: Hypocalcemia is still a common post-operative consequence following total thyroidectomy, generating potentially serious symptoms and concern in patients and lengthening hospital stays. This study was conducted to evaluate the risk factors for post-operative hypocalcemia after thyroid surgery.Methods: In this study, 60 patients who underwent thyroidectomy were included. Patients with concomitant lymph node dissection and hypocalcemia were excluded from the study. Serial serum calcium measures were taken and information about the operation, such as the patient's age and gender, whether the inferior thyroid artery was ligated or not, and the pathological report.Results: In 60 patients, 17 patients were had post-operative hypocalcemia. 3 in 5 patients (60%) with Hashimoto thyroiditis had hypocalcemia, followed by toxic multinodular goiter (MNG) (37.5%), thyroid adenomas (33.33%) and Graves’ disease (33.33%) had hypocalcemia after thyroidectomy.Conclusions: To conclude, hypocalcemia is a common side effect of total thyroid surgery, and it is caused by the unintentional removal of parathyroid glands or injury or spasm of the blood arteries that supply them.

Stopping Levothyroxine Therapy in Subclinical Hypothyroidism, Perhaps We Could Start a Trend

Introduction: Subclinical hypothyroidism (SCH) is diagnosed based on elevated thyrotropin (TSH) and normal thyroxine (FT4) levels. Previous guidelines recommended treatment of SCH with levothyroxine (LT4) when TSH is &gt; 10 uIU/mL or if TSH &lt;10 uIU/mL with symptoms suggestive of hypothyroidism, positive thyroperoxidase antibodies (TPO Ab) or evidence/risk factors of cardiovascular disease. There has been an increasing practice of LT4 prescription for SCH, which contributes to making LT4 the second most prescribed drug in the US. Case: This case reviews the course of a patient with SCH treated with LT4. A 68 year old woman with medical history of hyperlipidemia, osteoporosis, and non-toxic multinodular goiter was diagnosed with SCH due to Hashimoto’s thyroiditis based on TSH 9.59 uIU/mL (0.34 - 5.60), FT4 0.66 ng/dL (0.58 - 1.64), and +TPO Ab. The patient had similar thyroid function tests (TFT) 1 year ago. She reported symptoms of hair loss, dry skin, and fatigue. She decided to undergo a trial of LT4 50 mcg daily. Two months later, her TSH had normalized and she reported slight improvement of fatigue. After one year on LT4, the patient reported symptoms of anxiety and heat intolerance and decided to stop LT4. Laboratory work up revealed TSH 0.22 uIU/mL and FT4 1.03 ng/dL consistent with exogenous hyperthyroidism. At the time of her follow up, the patient had been off LT4 for about 3 weeks. She continued to have ongoing fatigue, but reported resolution of the hyperthyroid symptoms. She was advised to stay off LT4 and to have yearly TFT. Discussion This case illustrates that not only LT4 treatment for SCH did not result in apparent improvement of hypothyroid-related symptoms, but also caused iatrogenic hyperthyroidism. A recent meta-analysis of 21 randomized clinical trials including 2192 patients with SCH found that LT4 therapy is not significantly associated with improvement in general quality of life or thyroid-related symptoms. Additionally, there is evidence of potential harm associated with LT4 and added burden of lifelong management. In 2019, a new guideline panel issued a strong recommendation against thyroid hormones in adults with SCH. Patients who are already on LT4 therapy for SCH may benefit from LT4 deprescribing. Clinicians need to discuss with their patients if LT4 discontinuation is a reasonable consideration. Studies at low risk of bias assessing patient important outcomes after LT4 discontinuation are required imminently.

A Higher Cutoff for TSI Would Better Predict Recurrence in Patients With Graves’ Disease?

Introduction: GD is an autoimmune disease mediated by immunoglobulins (Igs) that activate TSH receptor (rTSH). Relapse after withdrawal of antithyroid drugs (ATD) can reach 60%. Measurement of TSH receptor antibodies (TRAb) and thyroid stimulating immunoglobulin (TSI) could be an indirect indicator of GD activity. TRAb assays measures thyroid-stimulating, thyroid-blocking and neutral Igs; TSI assays measures only stimulating Igs. Objetive: Evaluate, prospectively, autoimmunity before and after ATD therapy for thyrotoxicosis through TSI measurement. Methods: Patients were evaluated at the first visit and at the time of ATD withdrawal. TSH, thyroid hormones, TPO antibody, thyroglobulin antibody, and TRAb were measured using eletrochemiluminescent assays Roche Diagnostics; TSI was determined by chemiluminescent assay Siemens Diagnostics. According to manufacturers, TRAb &lt; 1.75 IU/L and TSI &lt; 0.55 IU/L were negative. Results: Sixty-seven patients mean age 45,7±2,45 years, 65 women, were evaluated: 50 at the first visit, 40 (80%) with GD, and 10 (20%) with toxic multinodular goiter (TMNG). TSI diagnostic sensitivity (Sen%) and specificity (Spe%) to diagnose GD were 90% and 100% respectively, similar to that of TRAb, of 89% and 100%. Thirty-six patients were evaluated for recurrence after suspension of ATD (19 of them also had the initial assessment): 21 (58.3%) did not present recurrence in an mean period of 9.5±2.1 months (3-18); and 15 (41.7%) relapsed in 4.4±2.6 months (2-12). In 10/21 patients who did not relapse, and whose TRAb was negative, TSI was positive at low levels, which was responsible for the low Spe% of this test. Assessing possible other cutoff points for the TSI in the recurrence assessment, an adjustment to 1.4 (TSI &lt;1.4 IU/L = negative) raised the Spe% to 86%. Conclusions: In this group, TSI and TRAb were equivalent for GD diagnosis. Many clinical factors have been suggested and TRAb measurement is known to be useful for predicting GD relapse because of the active pathogenic role of TRAb. For predicting recurrence, with the proposed cutoff point proposed by the kit manufacturer for TSI, a better sensitivity was obtained when compared with TRAb (93% versus 67%), despite very low specificity (38%); by raising the cutting point to 1.4 specificity could be increased to 86% without reduced sensitivity. A larger sample in needed to support a higher TSI cutoff point in the clinical routine for the assessment of GD recurrence after ATD.

Navigating the Debate on Large (4+cm) Thyroid Nodules: Local Insight on a Persisting Problem

Background: Thyroid nodules are a common clinical finding, however discordant practice guidelines for managing large nodules may result in unnecessary surgeries and excess costs. Recent data suggest similar false negative rates in fine needle aspiration (FNA) biopsies between small (&lt;4cm) and large (4+ cm) nodules, indicating that monitoring rather than surgery may be appropriate for large nodules. Evaluating current management strategies may reveal insights regarding excess surgeries, costs and opportunities for improvement. Objectives: The goal of this project was to describe the patients at our institution with large thyroid nodules and determine the proportion of potentially unnecessary surgeries and the associated predictors. Methods: This was a retrospective cohort study that included patients who received a FNA of nodule (s) ≥4cm between 11/1/2014 and 10/31/2019 at our tertiary care institution. Patient demographics, sonographic nodule size, fine needle aspiration cytology, molecular testing results, final surgical pathology, history of neck irradiation, family history of thyroid cancer, presence of compressive symptoms or presence of a toxic nodule or toxic multinodular goiter, were compared between patients who had surgery and those who did not. A surgery was considered inappropriate if the FNA result was benign in the absence of any of the following: a suspicious result on molecular testing, compressive symptoms, family history of thyroid cancer in a first degree relative, history of neck irradiation, toxic nodule or toxic multinodular goiter or substernal extension. Continuous variables were evaluated using Wilcoxon rank-sum test while categorical variables were tested using chi-square or Fisher’s exact test. Results: A total of 177 patients had a 4+ cm nodule during the timeframe. Half of patients (54.2%)with 4+ cm nodules had surgery. Patients who underwent surgery were significantly younger (51.5 years vs 62 years; P&lt;0.001), more likely to report obstructive symptoms (34.4% vs 12.1%; P=0.001) and have a larger nodule size (5.0 cm vs 4.7 cm; P=0.26) than patients who did not have surgery. Forty-one patients with benign (Bethesda II) FNA results went on to have surgery. All 41 patients were found to be negative at surgery, yielding a false negative rate of 0.0% in our cohort. Twenty-three surgeries (24.0%) were considered inappropriate and overall 13% (23/177) of patients with 4+cm nodules had unnecessary surgery. The median charge for these surgeries was $13,183. Conclusion: Approximately half of our patients with 4+ cm nodules had surgery, especially patients who are younger, report obstructive symptoms, and have larger nodule sizes. Overall 13% of our patients with 4+cm nodules had unnecessary surgery revealing opportunities for improving care and costs.