Cytomorphologic analysis of dyshormonogenetic goiter.

Dyshormonogenetic goiter is a rare cause for congenital hypothyroidism because of the lack of enzymes needed for the synthesis of thyroid hormones. They are usually treated with hormonal treatment. Cytomorphological features can lead to misdiagnosis of malignancy. Elaboration on the cytomorphological features of dyshormonogenetic goiter is scarce, with only four case reports in the literature. We present a case of a child with dyshormonogenetic goiter, highlighting its cytological features, and common differential diagnosis. We also compared cytomorphologic features with other cases reported in the literature.

Congenital hypothyroidism and thyroid dyshormonogenesis: a case report of siblings with a newly identified mutation in thyroperoxidase.

BACKGROUND: Thyroid dyshormonogenesis continues to be a significant cause of congenital hypothyroidism. Over time, forms of thyroid dyshormonogenesis can result in goiter, which can lead to difficult management decisions as the pathologic changes can both mimic or lead to thyroid cancer. METHODS: Herein we describe the cases of two brothers diagnosed with congenital hypothyroidism, with initial findings consistent with thyroid dyshormonogenesis. One brother eventually developed multinodular goiter with complex pathology on biopsy, resulting in thyroidectomy. RESULTS: Whole exome sequencing revealed the brothers carry a novel frameshift mutation in thyroperoxidase; the mutation, while not previously described, was likely both deleterious and pathogenic. Conlcusions: These cases highlight the complex pathology that can occur within thyroid dyshormonogenesis, with similar appearance to possible thyroid cancer, leading to complex management decisions. They also highlight the role that a genetic diagnosis can play in interpreting the impact of dyshormonogenesis on nodular thyroid development, and the need for long-term follow-up in these patients.

Large thyroid cyst in a patient with congenital hypothyroidism / Grande cisto tiroidiano em paciente com hipotireoidismo congênito

Thyroid hormone biosynthetic defects are rare causes of congenital hypothyroidism. Although, initial presentations are usually diffuse goiter and hypothyroidism, subsequently they may develop thyroid nodules and or thyroid cancer. We describe a case of hypothyroidism due to dyshormonogenesis whose one of the previously solid nodules degenerates into a large cyst. A 22-year-old male was referred to our clinic for evaluation of enlarging thyroid nodule. Hypothyroidism was diagnosed in infancy, however due to poor compliance to treatment TSH values were elevated most of the times. When he was fifteen the first nodule was detected which was a solid cold nodule. Fine needle aspiration was in favor of benign follicular nodule. Seven years later we found a large multi nodular thyroid with a predominant large cyst corresponding to the previously detected solid nodule. 21cc straw colored fluid was aspirated. Cytology was reported as benign cystic nodule. The patient underwent thyroidectomy and pathology confirmed a benign thyroid cyst. Although underreported thyroid dyshormonogenesis may progress to cystic degeneration. Taking into account the risk of malignancy and eventually cyst formation, we recommend more frequent evaluation in the face of nodule formation in these patients. Arq Bras Endocrinol Metab. 2014;58(9):958-61.

Os defeitos de biossíntese do hormônio tiroidiano são causas raras de hipotireoidismo congênito. Embora as apresentações iniciais sejam geralmente bócio difuso e hipotireoidismo, nódulos tiroidianos ou câncer de tiroide podem se desenvolver subsequentemente. Descrevemos aqui um caso de hipotireoidismo causado por disormonogênese e no qual um dos nódulos sólidos degenerou em um grande cisto. Um homem de 22 anos de idade foi encaminhado para nossa clínica para avaliação do aumento de um nódulo tiroidiano. O hipotireoidismo foi diagnosticado na infância. Entretanto, em razão da baixa conformidade ao tratamento, os valores de TSH estavam elevados na maior parte do tempo. Quando o paciente tinha 15 anos de idade, um primeiro nódulo sólido e frio foi detectado. A aspiração por agulha fina mostrou um nódulo folicular benigno. Sete anos depois encontramos múltiplos nódulos na tiroide e um grande cisto predominante que correspondia ao nódulo sólido anteriormente detectado. Foram aspirados 21cc de fluido cor de palha. A citologia mostrou um nódulo cístico benigno. O paciente foi submetido à tiroidectomia e o exame histopatológico confirmou um cisto tiroidiano benigno. Embora não seja comumente relatada, a disormonogênese da tiroide pode progredir para a degeneração cística. Ao serem considerados o risco de malignidade e a eventual formação de cistos, recomendamos uma avaliação mais frequente da formação de nódulos nesses pacientes. Arq Bras Endocrinol Metab. 2014;58(9):958-61.

Large thyroid cyst in a patient with congenital hypothyroidism.

Thyroid hormone biosynthetic defects are rare causes of congenital hypothyroidism. Although, initial presentations are usually diffuse goiter and hypothyroidism, subsequently they may develop thyroid nodules and or thyroid cancer. We describe a case of hypothyroidism due to dyshormonogenesis whose one of the previously solid nodules degenerates into a large cyst. A 22-year-old male was referred to our clinic for evaluation of enlarging thyroid nodule. Hypothyroidism was diagnosed in infancy, however due to poor compliance to treatment TSH values were elevated most of the times. When he was fifteen the first nodule was detected which was a solid cold nodule. Fine needle aspiration was in favor of benign follicular nodule. Seven years later we found a large multi nodular thyroid with a predominant large cyst corresponding to the previously detected solid nodule. 21cc straw colored fluid was aspirated. Cytology was reported as benign cystic nodule. The patient underwent thyroidectomy and pathology confirmed a benign thyroid cyst. Although underreported thyroid dyshormonogenesis may progress to cystic degeneration. Taking into account the risk of malignancy and eventually cyst formation, we recommend more frequent evaluation in the face of nodule formation in these patients.

Papillary carcinoma of the thyroid developed in congenital dyshormonogenetic hypothyroidism without goiter: Diagnosis by FNAB.

A 5-year-old girl known to have congenital dyshormonogenetic hypothyroidism since birth and under appropriate treatment (without goiter) developed a thyroid nodule which was found in the clinical follow-up. Fine-needle aspiration biopsy of the nodule allowed to diagnose a papillary thyroid carcinoma, a diagnosis which was certified by the surgical specimen exam. Dyshormonogenetic goiter may rarely associate with thyroid carcinoma. The present case appears unique since goiter was not present.

Congenital nephrotic syndrome and persistent hypothyroidism after bilateral nephrectomy.

Congenital nephrotic syndrome is commonly associated with hypothyroidism. Thyroid hormone supplementation is recommended as standard of care. The hypothyroidism is postulated to occur secondary to chronic massive proteinuria with loss of thyroid binding globulin, thyroid hormone and iodine. Previous reports have indicated that thyroxin may be discontinued following bilateral nephrectomy. We report our experience with one child with congenital nephrotic syndrome, Finnish type, and hypothyroidism who had a high requirement for thyroxin (100-150 microg/d) from infancy to 4 years of age. Hypothyroidism persisted despite bilateral nephrectomy and later following renal transplantation. However, his thyroxin requirement is now substantially lower (62.5 microg/d) at age 14 years. No goiter was detected clinically and antithyroid antibodies were negative. Thyroid ultrasound and 123I scan revealed a thyroid gland in the anatomically normal location. 123I uptake was elevated, 18% at 6 hours and 51% at 24 hours (normal values: 3-16% at 6 hours and 8-25% at 24 hours). Perchlorate was unavailable for a perchlorate washout study. We speculate that this patient may have an intrinsic problem with thyroid hormone synthesis. It is unclear whether this is related or coincidental to the Finnish nephrotic syndrome. We recommend following thyroid functions closely if thyroxin is discontinued following bilateral nephrectomies in Finnish type congenital nephrotic syndrome.

Congenital primary hypothyroidism with subsequent adenomatous goiter in a Turkish patient caused by a homozygous 10-bp deletion in the thyroid peroxidase (TPO) gene.

OBJECTIVE: Congenital primary hypothyroidism occurs in 1 of 4000 births. Whereas the majority of the cases are due to developmental defects of the thyroid gland, 20% carry a defect in thyroid hormonogenesis. We report a Turkish boy who had goitrous hypothyroidism due to a mutation in the thyroid peroxidase (TPO) gene. DESIGN: The TPO gene was sequenced directly from genomic DNA and cDNA which was transcribed from three RNA samples harvested from different parts of the patient's excised thyroid gland. Patient The boy was thyroidectomized because of continuing growth of his thyroid gland and development of multiple nodes suspected of malignancy by ultrasound examination. Histopathological examination verified a dyshormonogenetic goiter with multiple follicular adenomas. RESULTS: The patient had a novel homozygous 10-bp deletion of the TPO gene at position 2812 in exon 16. This frame shift mutation results in a severely altered intracellular part of the protein. The deletion identified in leucocyte DNA was also found in thyroid tissue cDNA - so that instability of the transcript or a splicing defect was excluded. Both unaffected parents were heterozygous carriers of the mutation whereas 50 healthy individuals of the same ethnic background did not harbour the mutation. CONCLUSIONS: The identified TPO gene deletion is the first mutation coding for an inactive TPO molecule, which has a severely altered intracellular segment. Because the most likely reason for the enlarging goiter was poor compliance of the patient, this report underlines the importance of a careful and regular follow-up of patients with dyshormonogenesis.