Thyroidology and public health: Challenges within the medical profession Sanjay Kalra Thyroid Research and Practice 2019 16(3):93-94

Assessment of serum midkine level in benign and malignant thyroid nodules. Can midkine be a marker of thyroid malignancy? Nermin Ahmed Sheriba, Maram Mohamed Mahdy, Rana Hashem Ibrahim Elattary, Maha Mohamed El-Nabarawy Thyroid Research and Practice 2019 16(3):95-99 Background: Thyroid nodules are a common clinical problem. The prevalence of malignancy in thyroid nodules is currently about 5%–15%. Fine-needle aspiration biopsy (FNAB) has improved the preoperative prediction of malignancy, but still has disadvantages including operator variability and nondiagnostic reports. Midkine (MK) is a novel heparin-binding growth factor; MK levels have been proposed as indicative of malignancy in numerous tumors. MK overexpression in thyroid cancer has been reported to be in correlation with clinicopathological features of the tumor, hypothesizing that MK might play a role as a biomarker for diagnosis and more aggressive behavior of thyroid cancer. Aim: The aim of this study is to evaluate the value of serum MK (SMK) as a marker of malignancy in patients with nodular thyroid disease. Patients and Methods: The current study included 75 individuals with age ranging from 25 to 80 years divided into 25 with malignant thyroid nodule (Group A), 25 with benign thyroid nodule (Group B), and 25 healthy individuals as a control group (Group C). Free triiodothyronine, free thyroxin, thyroid-stimulating hormone, and SMK levels were assessed. Individuals with thyroid nodules were submitted for neck ultrasonography and FNAB. Results: On comparing the three studied groups, a high statistically significant difference in plasma MK levels was found (P < 0.001), being higher in Group A (malignant nodule) with a mean of 1.127 ± 0.527 than Group B (benign nodule) with a mean of 0.536 ± 0.301 with P < 0.001* and also higher in Group A (malignant nodule) with a mean of 1.127 ± 0.527 than Group C (control) with a mean of 0.366 ± 0.230 with P < 0.001*. There was significant difference regarding MK levels, with thyroid nodule contour being higher in thyroid nodule with irregular contour than thyroid nodule with regular contour (P < 0.001*) and calcification being higher in microcalcification than macrocalcification (P = 0.006*). There was high statistically significant difference regarding the level of MK between papillary carcinoma and follicular carcinoma (P < 0.001*). Conclusions: SMK might be the indicator of malignant thyroid cytopathology, suggesting that MK might serve as a novel biomarker in the assessment of thyroid nodules. The present study explored the usefulness of MK as a biomarker in the differentiation between benign and malignant thyroid nodules in samples from serum.

Morphological variations of the thyroid gland: An insight on embryological and clinicoanatomical considerations Honnegowda Thittamaranahalli Muguregowda, G Krishna, KG Prakash Thyroid Research and Practice 2019 16(3):100-104 Background: The thyroid gland, a highly vascular endocrine gland, is composed of two lateral lobes connected by isthmus. A wide range of morphological alterations of the thyroid gland such as hypoplasia, ectopy to hemiagenesis, and genesis are common because of disturbed embryogenesis. The significance of diagnosing such extensions of the thyroid gland is crucial. It may alter the normal anatomical relationship of the thyroid gland with other adjacent cervical structures. Further, it may be confused with a tumor mass on magnetic resonance imaging and scintillation scans. Methods: The primary aim is to study the thyroid gland for gross anatomical variations (weight, height, and breadth) and secondarily to document the morphometric and congenital/developmental variation gross of the thyroid gland in 65 cadavers from the coastal belt of South India. The glands were according to the various age groups of the cadavers. Results: The mean thyroid weight was 26.01 ± 7.14 g. In males, it was 26.59 ± 6.96 g, whereas in females, it was 20.93 ± 8.98 g. The pyramidal lobe was present in 35 (53.8%), and the presence of the levator glandulae thyroideae was noted in 25 (38.48%) of male cadavers. Agenesis of the isthmus was found in 20 (30.76%). However, the accessory thyroid tissue was found in only one female cadaver. Conclusions: Our morphometric study on cadaveric thyroid glands highlights individual and ethnic variations. Knowledge of various developmental anomalies and unusual variations of the thyroid gland is of paramount importance to differentiate it from other pathologies such as autonomous thyroid nodule and thyroiditis.

Role of nuclear grooves in the cytological diagnosis of papillary carcinoma thyroid Archana S Bhat, Lisa Varma, Hilda Fernandes, CS Jayaprakash Thyroid Research and Practice 2019 16(3):105-107 Introduction: It is well known that nuclear grooves play a major role in the diagnosis of papillary carcinoma thyroid (PCT). Furthermore, grooves are found in many nonneoplastic lesions of thyroid. Aims: The aim of this study is to calculate the percentage of nuclear grooves in histopathologically proven cases of papillary carcinoma and nonneoplastic lesions (Hashimoto's thyroiditis and colloid goiter). Materials and Methods: This retrospective study was carried out by reviewing the data and cytology smears of 21 histopathologically confirmed cases of PCT and 10 cases each of Hashimoto's thyroiditis and colloid goiter. The percentage of nuclear grooves was calculated in oil immersion by counting 100–500 cells depending on the cellularity. Results: The percentage of nuclear grooving ranged from 15% to 85% in the papillary carcinoma cases. Greater than 20% nuclear grooves were observed in 19 (90.4%) of the cases. Nuclear crowding and overlapping, pale chromatin, nuclear grooves, nuclear enlargement, and prominent nucleoli were seen in all (100%) cases. Intranuclear cytoplasmic pseudoinclusions were seen in only 5 (23.8%) of the cases. Histiocytes, metaplastic cells, and multinucleated giant cells were seen in 12 (57.1%), 10 (47.6%), and 6 (28.5%) of the cases. The percentage of nuclear grooves in nonneoplastic cases overall observed was <10%. The sensitivity and specificity of grooves for PCT at ≥20% were 90.5% and 100%, respectively. Conclusion: Whenever in doubt, a diagnosis of papillary carcinoma can be offered confidently by this semiquantitative approach for grooves in combination with other features.

Iodine nutrition status in Graves' disease: A single-center study from Bangladesh Md Abu Jar Gaffar, A B. M. Kamrul-Hasan, Afsar Ahammed, Muhammad Abul Hasanat, Md Fariduddin Thyroid Research and Practice 2019 16(3):108-112 Context: An increase in occurrence of Graves' disease (GD) has been reported in many countries after the introduction of the salt iodization program. Aims: To observe iodine nutrition status in GD. Settings and Design: Cross-sectional observational study conducted in the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from May 2013 to September 2014. Methods and Material: This study included 140 GD patients (55 newly detected, 85 already under treatment). Urinary iodine concentration (UIC) was measured in spot urine sample following wet digestion method. The iodine nutrition status was categorized according to the internationally recommended cutoffs of UIC (excessive: ≥300 μg/L, more than optimal: 200-299 μg/L, optimal: 100-199 μg/L, deficiency: <100 μg/L). Results: The median UIC in subjects with Graves' disease was 96.69 μg/L. 21.2% of the study subjects had iodine status to be considered as more than optimal or excessive, 25.7% had optimal iodine level, and more than half (51.4%) had iodine deficiency. The mean UIC were similar in newly diagnosed and treated groups, and among subjects with different thyroid functional status. UIC did not differ among male and female subjects and among subjects from different socioeconomic groups. UIC showed no correlations with age, socioeconomic condition, the family history of thyroid disease, TSH, FT4, and thyroid function status of the study participants. Conclusions: Effective monitoring of salt iodization program is needed to prevent iodine-excess related increase in the prevalence of Graves' disease.

Prognostic efficacy of thyroid profile with sequential organ failure assessment score in predicting mortality in intensive care unit patients Arvind Mishra, Rohin Saini, Madhukar Mittal, Dandu Himanshu, Kamlesh Kumar Gupta, Abbas Ali Mahdi Thyroid Research and Practice 2019 16(3):113-120 Introduction and Objectives: Thyroid hormone changes in critically ill patients are commonly observed phenomenon. This is known as sick euthyroid syndrome. Sequential organ faillure assessment (SOFA) score is used to track and determine the extent of a person's organ function or its rate of failure. We performed a prospective observation study to analyze the prognostic rather than diagnostic efficacy of thyroid function test (TFT) (T3, T4, thyroid-stimulating hormone [TSH], free triiodothyronine [fT3], and free thyroxine [fT4]) in unselected critically ill patients and compare the prognostic efficacy of fT3, fT4, TSH, T3, and T4 with SOFAS in predicting mortality in critically ill patients. Materials and Methods: We studied a sample of unselected 338 patients admitted in the intensive care unit (ICU) and measured their TFT, routine biochemical parameters within 48 h of admission along with SOFA scores and assessed their individual and combined efficacy in predicting mortality. All patients with known thyroid illness were excluded from this study. Results: There were 200 survivors and 138 nonsurvivors, the nonsurvivors had higher SOFAS score and lower free T3 levels and lower T3 levels compared to survivors. ICU survival was predicted using SOFAS score alone and a combination of TFT with SOFA score. Conclusions: In critically ill patients with higher SOFA score, lower values of serum fT3 and T3 levels were clinically significantly associated with mortality and free T3 have additional powers to improve predictive ability to SOFAS in predicting mortality in ICU patients.

Severe hypothyroidism-associated acute renal failure – A case series from North India and review of literature Namrata S Rao, Abhilash Chandra, Kiran Preet Malhotra Thyroid Research and Practice 2019 16(3):121-127 Background: Several cases of complete or partially reversible renal failure have been reported in association with severe hypothyroidism, which have responded to thyroxine replacement. However, its risk factors, pathology, pathophysiology, and time of recovery remain unclear. Aim: We report our experience with 31 cases of renal failure in association with severe hypothyroidism, from a goiter-endemic belt in North India, along with a review of existing literature. Materials and Methods: We retrieved cases presenting to our centre, from August 2013 to April 2018 and collected information regarding clinical presentation, laboratory parameters including renal and thyroid function tests, creating kinase, urinary findings and follow-up data pertaining to time and extent of renal function recovery. In three cases, renal biopsies were also done, and these were reviewed by a pathologist. Results: In our study, females slightly outnumber males. More than one-third of patients were known hypothyroid and had defaulted on medications. The severity of serum thyroid-stimulating hormone and CK elevation were not associated with the severity of renal failure or its extent or time of recovery. Older age, coexistence of diabetes mellitus and/or hypertension, higher serum creatinine at presentation, and urinary abnormalities (proteinuria and/or active sediments) correlated significantly with lack of complete renal recovery. All the three biopsies revealed significant tubulointerstitial fibrosis. Conclusions: Thyroid function tests should be performed in the evaluation of unexplained renal failure, even in cases with underlying chronic kidney disease. It is also an important preventable cause of renal failure in known hypothyroid patients.

A case-based approach to aggressive variants of papillary thyroid carcinoma with literature review Joseph Antoine Flordelis Chatto, Annette Laurente Salillas Thyroid Research and Practice 2019 16(3):128-136 Papillary thyroid caarcinoma (PTC) is the most common thyroid and endocrine malignancy. Although considered to be indolent, aggressive variants have been identified, including the Tall Cell (TCV), Columnar Cell (CCV), Hobnail (HPTC) and Solid Variants (SVPTC). The objective of this study is to pre-operatively recognize the cytologic features of these variants. Four cases with final diagnoses of TCV, CCV, HPTC and SVPTC were reviewed and compared with Fine Needle Aspiration Biopsy (FNAB) smears. The first case is a 44-year-old female diagnosed with TCV pre-operatively through FNAB and was confirmed through tissue biopsy showing malignant glands in papillary formation with greater than 50% of tall cells. The second patient is a 54-year-old female with CCV showing stratified columnar cells with cytoplasmic supranuclear and subnuclear vacuoles. Third is a 57-year-old female with HPTC exhibiting eccentrically-located nuclei imparting a hobnail appearance with cellular dyscohesiveness. The fourth case is a 59-year-old female diagnosed with SVPTC showing predominantly solid sheets surrounded by thin, delicate fibrous stroma. They all have nuclear features of PTC. TCV, CCV, HPTC and SVPTC are related to extrathyroidal extension, angiolymphatic invasion, positive surgical margin and lymph node metastasis. FNAB is an important tool to recognize these variants preoperatively and plan for amore comprehensive management.

Extensive squamous metaplasia in papillary carcinoma of the thyroid: A potential diagnostic pitfall Subhash Yadav, Rajiv Kumar, Munita Bal, Asawari Patil Thyroid Research and Practice 2019 16(3):137-139 It is a rare event to find squamous cells in the thyroid gland. Squamous metaplasia (SM) of the thyroid follicular epithelium is one of such conditions. SM can occur in association with nonneoplastic as well as neoplastic thyroid lesions. Here, we report a case of papillary carcinoma of the thyroid in a 26-year-old female showing extensive SM. On immunohistochemistry, squamous as well as papillary carcinoma component expresses CK7 and thyroglobulin. High molecular weight cytokeratin and p63 were positive in only in the squamous area, while TTF-1 was negative in these cells. Extensive SM in the thyroid can be misinterpreted as primary or metastatic squamous cell carcinoma. Further, the tumor may be mislabeled as collision tumors of thyroid. As it might lead to therapeutic implications, the distinction of SM in thyroid is necessary.

Diagnostic issue and caveats of immunoreactivity for Ki67 in hyalinizing trabecular neoplasm with a review of literature Veer Karuna, Priya Gupta, Mamta Gupta, Kriti Grover Thyroid Research and Practice 2019 16(3):140-143 Few benign and malignant tumors of thyroid lesion share many histological features, including papillary and trabecular pattern, hyalinized stroma, calcification, nuclear grooving, and nuclear inclusion. The lesions those have these common features are hyalinizing trabecular tumor, papillary thyroid carcinoma, medullary carcinoma, paraganglioma, trabecular follicular adenoma (TFA), and poorly differentiated tumor (PDT). These tumors are derived from thyroid follicular cell except PDT and paraganglioma. Hyalinized trabecular tumor and TFA are rare tumors. Due to these common features, they create a diagnostic pitfall for a false-positive or false-negative diagnosis. Therefore, histopathological and immunohistochemical studies are needed to make a definite diagnosis. The present case describes a relatively rare thyroid tumor – hyalinizing trabecular tumor – with its varied morphological features creating diagnostic difficulties and role of immunohistochemistry in formulating definitive diagnosis.