Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics.

Objective: Mutations in DICER1 are found in differentiated thyroid carcinoma (DTC) and in multinodular goiter (MNG) at a younger age with other tumors, which characterizes DICER1 syndrome. DICER1 is one driver to DTC; however, it is also found in benign nodules. We speculated that patients with mutations in DICER1 may present long-lasting MNG. Our aim was to investigate the frequency of DICER1 variants in patients with MNG. Subjects and methods: Patients who submitted to total thyroidectomy due to large MNG with symptoms were evaluated. DICER1 hotspots were sequenced from thyroid nodule samples. To confirm somatic mutation, DNA from peripheral blood was also analyzed. Results: Among 715 patients, 154 were evaluated with 56.2 ± 12.3 years old (28-79) and the thyroid volume was 115.7 ± 108 mL (16.2-730). We found 11% with six DICER1 variations in a homo or heterozygous state. Only rs12018992 was a somatic DICER1 variant. All remaining variants were synonymous and likely benign, according to the ClinVar database. The rs12018992 was previously described in an adolescent with DTC, measuring 13 mm. There were no significant differences according to gender, familial history of goiter, age, thyroid volume, TSH and TI-RADS classification between DICER1 carriers. Free T4 were lower in patients with DICER1 polymorphisms (13.77 ± 1.8 vs. 15.44 ± 2.4 pmol/L, p = 0.008), regardless of TSH levels. Conclusion: We conclude that germline DICER1 variants can be found in 11% of large goiters but no second-hit somatic mutation was found. DICER1 is one driver to thyroid lesion and a second-hit event seems unnecessary in the MNG development.

Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Analysis of clinical characteristics of thyroid phenotype in Pendred syndrome based on multiple databases.

OBJECTIVE: This study aimed to provide statistical data support for the development of thyroid phenotype-related follow-up and reference for follow-up duration and project selection by analyzing the clinical characteristics of thyroid phenotype in Pendred syndrome (PDS) based on multiple databases. MATERIALS AND METHODS: PDS-related pathogenic or possibly/pathogenic mutations were searched by Deafness Variation Database (DVD), ClinVar, and PubMed databases, the mutation sites were counted and the characteristics and thyroid phenotypes were analyzed. RESULTS: The median age of hearing phenotype onset in PDS cases reported in multiple databases was 1.0 (1.0, 2.0) years, the median age of thyroid phenotype onset was 14.5 (5.8, 21.0) years, and the median age that thyroid phenotype was more delayed than hearing phenotype was 10.0 (4.0, 17.0) years. There were significant differences in the distribution of onset time between the two phenotypes (Z=-4.560, p<0.01). In these patients, the positive rates of goiter, thyroid nodules, abnormal thyroid function, and perchlorate discharge test (PDT) were 78%, 78%, 69%, and 78%, respectively. Moreover, the number of thyroid phenotype-positive items in the genotype group with frameshift mutation was not significantly higher than that in the group without frameshift mutation (Z=-1.452, p=0.147). CONCLUSIONS: The early missed diagnosis of PDS may be due to the late onset of thyroid phenotype and the non-100% positive rate of examination items. Therefore, multi-item follow-up of the thyroid gland into adulthood will benefit patients. At present, the relationship between genotype and phenotype is still unclear, and prognosis cannot be determined according to genotype.

Ectopic intrapulmonary thyroid masquerading as metastatic carcinoma of the lung: a rare case scenario.

BACKGROUND: The intrapulmonary ectopic thyroid gland is exceedingly rare since the ectopic thyroid was discovered. Only eight cases have been reported in the worldwide literature. We present a case of multiple intrapulmonary ectopic thyroid glands with nodular goiter in a 10-year-old girl. CASE PRESENTATION: The girl was found with multiple intrapulmonary nodules in bilateral lungs during the treatment of nodular goiter. The intrapulmonary lesions were initially thought to be a high possibility of metastatic cancer. A computed tomography-guided percutaneous lung biopsy was performed, and the pathological examination confirmed that the diagnosis was ectopic intrapulmonary thyroid. CONCLUSION: The ectopic intrapulmonary thyroid should be considered when children with nodular goiter presenting with suspected metastases in the lung.

[Surgical treatment of a patient with stage v multinodular toxic goiter, severe thyrotoxicosis, strangulation syndrome and severe comorbidities]. / Khirurgicheskoe lechenie patsientki s mnogouzlovym toksicheskim zobom V stepeni, tireotoksikozom tyazheloi stepeni, kompressionnym sindromom i tyazhelymi soputstvuyushchimi zabolevaniyami.

The authors describe thyroidectomy in a patient with multinodular toxic goiter stage V, severe thyrotoxicosis complicated by thyro-cardiac disease, strangulation syndrome and severe comorbidities. Nodular euthyroid goiter was first diagnosed in 1992, and resection of the right thyroid lobe was performed. Progressive enlargement of thyroid gland and thyrotoxicosis occurred after coronavirus infection in February, 2020. Along with progression of thyrotoxicosis and strangulation of cervical organs, the patient suffered from portal vein thrombosis, pulmonary embolism. Myeloproliferative disease with essential thrombocythemia was also diagnosed. Volume of the right and left thyroid lobes was 69 and 101.3 cm3, respectively. X-ray examination of the esophagus revealed narrowing at C6 level up to 5-8 mm. Surgery time was 2 hours, dimension of removed right thyroid lobe - 10.0×7.5×6.5 cm, left thyroid lobe - 11.0×6.5×5.5 cm, total weight - 348 g. The patient was discharged in 6 days after surgery.

SLC26A4 mutation in Pendred syndrome with hypokalemia: A case report.

RATIONALE: Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss, inner ear malformations, goiter, and abnormal organification of iodide. It is caused by mutations in SLC26A4 gene, which encodes pendrin (a transporter of chloride, bicarbonate, and iodide). Pendred syndrome is a common cause of syndromic deafness, but the metabolic abnormalities it causes are often overlooked. Here, we report the case of a patient diagnosed with Pendred syndrome with hypokalemia. PATIENT CONCERNS: A 53-year-old deaf-mute woman was hospitalized due to severe limb asthenia. The emergency examination showed that her blood potassium level was 1.8 mmol/L. DIAGNOSES: Through the genetic test, we found a mutation of SLC26A4 gene in NM_000441: c.2027T>A, p.L676Q, as well as the SLC26A4 exon 5-6 deletion. These genetic variations pointed to Pendred syndrome (an autosomal recessive disorder that mainly affects the inner ear, thyroid, and kidney) which is a common cause of syndromic deafness. INTERVENTIONS: The patient was treated with potassium supplements and screened for the cause of hypokalemia. OUTCOMES: The patient was discharged after her potassium levels rose to the normal range. LESSONS: Patients with Pendred syndrome may also have certain metabolic abnormalities; thus, more attention should be paid to them during clinical diagnosis.

Katanin subunits p60 and p80, potential biomarkers for papillary thyroid carcinoma to distinguish nodular goiter: STROBE.

ABSTRACT: Katanin subunits p60 and p80 are involved in microtubule-mediated cytoskeletal organization during cell division. Their aberrant expression has been found in prostate, breast, and non-small cell lung (NSCLC) cancers. It has recently been reported that compared with adjacent papillary thyroid carcinoma (PTC) tissues, both are highly expressed in tumor tissues. Here, we investigated whether katanin subunits p60 and p80 can be used as potential biomarkers for PTC to distinguish nodular goiter (NG).Immunohistochemistry was performed to investigate the expression of katanin subunits p60 and p80 in the tissues of 97 cases of PTC and NG. This cohort included 87 cases with PTC (74 classical or conventional (CPTC) and 13 follicular (FVPTC) variants) and 10 cases with NG.We found that katanin subunits p60 and p80 were expressed in PTC, but not in NG. The cutoff values of katanin p60 and p80 for PTC were 22.43% and 0.83%, respectively. The katanin subunit p60 was significantly associated with lymph node metastasis. Katanin subunit p80 was more highly expressed in CPTC than in FVPTC. The expression of the katanin subunit p60 was positively correlated with the expression of katanin p80 in PTC. Importantly, we found that overexpression of katanin p60 increased the expression of katanin p80 in a human papillary thyroid carcinoma KTC-1 cell line, which further supports the existence of katanin p60 and p80 feedback loops.Our results indicate that katanin subunits p60 and p80 may be used as potential PTC biomarkers to distinguish NG and may be novel therapeutic targets for PTC.

Selfie-driven thyroid disease leads: A study on a unique sign and its utility in clinical practice.

Introduction: Taking a photograph of self alone or with a group called selfie, has become modern-day rage with spurt in smartphone technology. It has catapulted from a hobby into psychiatric ailment, especially among teens and young adults. Although it is considered a psychiatric ailment keeping them aloof from social interactions, we observed an inadvertent advantage in this process. In this context, we present some intriguing findings in this study. Materials and Methods: This retrospective study was based on compilation of 14 cases from endocrine surgery outpatient cum inpatient database collected over 2 years' period. The inclusion criteria are the chief complaint (CC) was noted only after watching the selfie picture and not otherwise; the CC leads them to consult physician; the picture was captured by oneself or other person who was also part of that image; and the CC leads to definitive diagnosis of thyroid disease requiring treatment. All other clinical, investigative, and treatment (medical and surgical) were studied. Results: In all, we had 14/5820 (0.0024%) cases meeting the above criteria. CC and later confirmed in pictures were four cases of Grave's disease associated ophthalmopathic exophthalmos, eight cases of goiter, and two cases of facial puffiness (myxedema related). All these CC helped in investigating for the diagnosis of Graves' disease (4), nodular goiter (8), and hypothyroidism (2) confirmed by appropriate investigations. Ten cases underwent thyroidectomy (two of the nodular goiter cases were papillary thyroid cancer) and four cases took conservative medical treatment. Conclusions: Although selfie is considered a modern-day lifestyle-induced psychiatric illness, it can inadvertently help in picking up thyroid diseases in earlier stages.

RésuméIntroduction: Prendre une photo de soi seul ou avec un groupe appelé selfie, est devenu une rage moderne avec une poussée dans le smartphone La technologie. Il est passé d'un passe-temps à une maladie psychiatrique, en particulier chez les adolescents et les jeunes adultes. Bien qu'il soit considéré comme un maladie psychiatrique les gardant à l'écart des interactions sociales, nous avons observé un avantage par inadvertance dans ce processus. Dans ce contexte, nous présentent des découvertes intéressantes dans cette étude. Matériels et méthodes: Cette étude rétrospective a été basée sur la compilation de 14 cas de Base de données de chirurgie endocrinienne ambulatoire et hospitalière collectée sur une période de 2 ans. Les critères d'inclusion sont la plainte principale (CC) a été noté seulement après avoir regardé la photo selfie et pas autrement; le CC les amène à consulter un médecin ; l'image a été capturée par soi-même ou une autre personne qui faisait également partie de cette image ; et le CC conduit au diagnostic définitif d'une maladie thyroïdienne nécessitant un traitement. Tous les autres clinique, d'investigation et de traitement (médical et chirurgical) ont été étudiés. Résultats : Au total, nous avons eu 14/5820 (0,0024%) cas répondant aux critères ci-dessus Critères. CC et confirmés plus tard en images étaient quatre cas d'exophtalmie ophtalmopathique associée à la maladie de Grave, huit cas de goitre, et deux cas de gonflement du visage (liés au myxoedème). Tous ces CC ont aidé à enquêter pour le diagnostic de la maladie de Graves (4), nodulaire goitre (8) et hypothyroïdie (2) confirmées par des examens appropriés. Dix cas ont subi une thyroïdectomie (deux des cas de goitre nodulaire étaient un cancer papillaire de la thyroïde) et quatre cas ont suivi un traitement médical conservateur. Conclusions : Bien que le selfie soit considéré comme un maladie psychiatrique induite par le mode de vie, il peut aider par inadvertance à contracter des maladies thyroïdiennes à un stade précoce. Mots-clés: endocrinien, exophtalmie, goitre, selfie, thyroide, thyroidectomie.

Poorly Differentiated Thyroid Carcinoma Coexisting with Graves' Disease Involving T3 Thyrotoxicosis due to Increased D1 and D2 Activities.

Background: Poorly differentiated thyroid carcinoma is rare and patients are typically euthyroid. We report a novel rare case of poorly differentiated thyroid carcinoma with triiodothyronine (T3) thyrotoxicosis. Patient's Findings: A 77-year-old man presented to Kuma Hospital due to a neck tumor. A thyroid ultrasonography revealed a 220-mL mass in the right lobe. Laboratory data showed low serum thyrotropin (TSH), low free thyroxine (fT4), and high free T3 (fT3) levels. Anti-TSH receptor antibodies and thyroid-stimulating antibodies were positive. 131I scintigraphy showed diffuse uptake only in the left thyroid lobe. The patient underwent a total thyroidectomy and histological examination identified as poorly differentiated thyroid carcinoma. He was diagnosed with poorly differentiated thyroid carcinoma coexisting with Graves' disease. The tumor showed elevated type 1 iodothyronine deiodinases (D1) and type 2 iodothyronine deiodinases (D2) activities compared with that of the left thyroid lobe. Summary and Conclusions: Increased D1 and D2 activities in poorly differentiated carcinoma resulted in T3 toxicosis with a high serum fT3/fT4 ratio.

DNA repair proteins may differentiate papillary thyroid cancer from chronic lymphocytic thyroiditis and nodular colloidal goiter.

Malignant thyroid lesions are the most common malignancy of the endocrine glands with increasing rates in the last two decades. Papillary thyroid cancer is the most common thyroid malignancy. In our study, we aimed to quantitatively evaluate the levels of DNA repair proteins MSH2, MLH1, MGMT, which are representative blocks of patients diagnosed with papillary carcinoma, chronic thyroiditis, or colloidal goiter. Total or subtotal thyroidectomy material of 90 patients diagnosed with papillary carcinoma, nodular colloidal goiter, or chronic thyroiditis between 2009 and 2012 were retrospectively evaluated. Tissue samples obtained from paraffin blocks were stained with MGMT, MSH2, MLH1 proteins and their immunohistochemistry was evaluated. Prepared sections were examined qualitatively by an impartial pathologist and a clinician, taking into account the staining method under the trinocular light microscope. Although there was no statistically significant difference in MGMT, MSH2, MLH1, follicular cell positivity, staining intensity, and immunoreactivity values, papillary carcinoma cases showed a higher rate of follicular cell positivity, and this difference was more pronounced between papillary carcinoma and colloidal goiter. In the MSH2 follicular cell positivity evaluation, the difference between chronic thyroiditis and colloidal goiter was significant (p = 0.023). The difference between chronic thyroiditis and colloidal goiter was significant in the MSH2 staining intensity evaluation (p = 0.001). The difference between chronic thyroiditis and colloidal goiter was significant in MLH1 immunoreactivity evaluation (p = 0.012). Papillary carcinoma cases were demonstrated by nuclear staining only for MSH2 and MLH1 proteins as opposed to hyperplastic nodules. The higher levels of expression of DNA repair genes in malignant tumors compared to benign tumors are attributed to the functional activation of DNA repair genes. Further studies are needed for DNA repair proteins to be a potential test in the development and progression of thyroid cancer.

Altered methylarginine levels after surgery in subjects with multinodular goiter.

OBJECTIVES: Thyroid disorders are important risk factor for cardiovascular diseases. Levels of methylarginines such as asymmetric dimethyl arginine (ADMA), L-monomethyl arginine (L-NMMA), symmetric dimethyl arginine (SDMA) are increase in cardiovascular diseases. Multinodular goiter (MNG) is the most common type of goiter in adults. To date, no study has been conducted to determine the levels of methylarginine in euthyroid MNG patients. Our aim in this study is to compare levels of methylarginines and related metabolites in the preoperative, postoperative MNG patients and controls. METHODS: Serum ADMA, SDMA, L-NMMA, homoarginine (hArg), arginine and citrulline concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: ADMA (p<0.001), L-NMMA (p=0.002), l-arginine (p=0.006) and citrulline (p<0.001) levels were statistically significantly higher in preop group than postop group. ADMA (p=0.003), L-NMMA (p=0.003) levels were statistically significantly higher and SDMA/ADMA (p<0.001), hArg/ADMA (p<0.001) levels were statistically significantly lower in preop group than control group. CONCLUSIONS: The levels of methylarginines and related metabolites altered in the euthyroid MNG patients compared to the control group, and more importantly, there were significant differences between the preop and postop groups. Therefore, these metabolites can be useful in the diagnosis and prognosis of thyroid disorders, even if thyroid hormone levels are normal.

Low level of plasma fibulin-1 in patients with thyroid lesions: a case-control study and literature review.

Investigating novel biomarkers discriminating thyroid nodules is a matter of great importance for differential diagnosis. The current study was planned to investigate the diagnostic value of fibulin-1 in plasma specimens of patients with thyroid nodules. A literature review was also performed to gain an understanding of the existing research relevant to the main role of fibulin-1 in carcinogenesis. In this case-control study, the levels of plasma fibulin-1 were compared in 82 subjects including papillary thyroid cancer (PTC; n = 30), multinodular goiter (MNG; n = 30), and healthy subjects (n = 22) using enzyme-linked immunosorbent assay (ELISA). Fibulin-1 levels of patients with PTC and MNG were documented to be significantly lower than those of healthy subjects (PTC vs. Healthy; P = 0.000, MNG vs. Healthy; P = 0.000). No statistically significant differences were found between PTC and MNG groups when fibulin-1 levels were compared (P > 0.05). Low level of plasma fibulin-1 was associated with an increased risk of PTC tumorigenesis (odds ratio = 0.810; 95% CI: 0.704-0.933; P = 0.003). Further, fibulin-1 had an appropriate diagnostic value for detecting PTC patients with a sensitivity of 73.33%, and specificity of 100% at the cutoff value > 4.9 (ng/ml). According to the results of the present research which are tied well with previous studies, the abnormal downregulation of fibulin-1 may play a role in the PTC and MNG tumorigenesis. In addition, fibulin-1 probably promotes the development and progression of other human cancer; however, further studies are needed to improve current understandings.

[Thyroid nodules: The Guidelines of the American Thyroid Association from a European Perspective]. / Schilddrüsenknoten: ATA-Leitlinie aus europäischer Sicht.

In Germany and in other regions with former iodine deficiency, thyroid nodules and nodular goiter are still much more frequent than in the U.S.A. The American Thyroid Association (ATA) has published 2015 revised guidelines for patients with thyroid nodules and differentiated thyroid cancer. For evaluation of suspected thyroid nodules the authors describe high, intermediate, low and very low suspicion pattern and recommend further fine needle aspiration cytology, depending on the pattern and the size of the nodule. The high suspicion pattern includes irregular margins of the nodule, which may be an important criterion for malignancy of solitary nodules. In nodular goiters with multiple nodules grown together and without clear margins, frequently observed in former iodine deficiency regions, irregular margins may not be a significant criterion for malignancy. Another pattern, hypoechogenicity, which is frequently seen in benign nodules in former iodine deficiency areas, is also not a clear criterion for malignancy. Only strong hypoechogenicity may indicate malignancy. Another difference relates to the recommendation of scintigraphy that according to the guideline is restricted to patients with decreased TSH. In regions with former iodine deficiency, it has been demonstrated that thyroid autonomy may be present even if TSH is in the lower normal range. Therefore, in Germany scintigraphy is recommended for preoperative evaluation of all patients with thyroid nodules or nodular goiter.

Thyroid gland changes in patients with acromegaly.

OBJECTIVE: Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. SUBJECTS AND METHODS: In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. RESULTS: Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. CONCLUSIONS: Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75.

Thyroid gland changes in patients with acromegaly

ABSTRACT Objective Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. Subjects and methods In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. Results Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. Conclusions Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75

Congenital chloride diarrhea and Pendred syndrome: case report of siblings with two rare recessive disorders of SLC26 family genes.

BACKGROUND: Congenital chloride diarrhea (CLD; OMIM 214700) is a rare autosomal recessive disorder caused by pathogenic variations in the solute carrier family 26 member A3 (SLC26A3) gene. Without salt substitution, this chronic diarrheal disorder causes severe dehydration and electrolyte disturbances. Homozygous variants in the nearby gene SLC26A4 disrupt anion exchange in the inner ear and the thyroid, causing Pendred syndrome (PDS; OMIM 274600), which is the most frequent form of syndromic deafness. CASE PRESENTATION: We report an unusual co-occurrence of two rare homozygous mutations in both the SLC26A3 and SLC26A4 genes, causing a rare combination of both CLD and PDS in two siblings. Although the clinical pictures were typical, the combined loss of these anion transporters might modulate the risk of renal injury associated with CLD. CONCLUSIONS: Familial presentation of two rare autosomal recessive disorders with loss of function of different SLC26 anion transporters is described. Independent homozygous variants in the SLC26A3 and SLC26A4 genes cause CLD and PDS in siblings, shedding light on co-occurrence of rare recessive traits in the progeny of consanguineous couples.

Presentations and Outcomes of Thyroid Storm.

The aim of this study is to describe the characteristics and outcome of thyroid storm patients presenting at two tertiary care centres of Karachi, i.e. at Dow University of Health Sciences; and Liaquat National Hospital, Karachi, from December 2018 to May 2019. All patients between 18-70 years of age, who were admitted with thyroid storm and fulfilled the Burch- Wartofsky criteria, were inducted. Demographics including age, gender, clinical presentations, systemic symptoms, clinical examination of the thyroid and laboratory findings were reviewed from the file records to identify factors associated with mortality using the available data. Overall, five (62.5%) out of eight patients were female. The mean age was 43 ±1.67 years. Infections were the most common comorbid condition followed by cardiovascular and gastrointestinal diseases. The in-hospital mortality rate was 87.5% (n=07).