Archives of Medicine and Health Sciences

: 2020  |  Volume : 8  |  Issue : 1  |  Page : 88--90

Dyshormonongenetic goiter: A rare and important entity

Yasmin Altaf Momin1, Sameer Ahmed A H. Ansari2,  
1 Department of Pathology, Grant Government Medical College, Mumbai, Maharashtra, India
2 Department of Pathology, King Hamad University Hospital, Al Sayh, Bahrain

Correspondence Address:
Dr. Sameer Ahmed A H. Ansari
Department of Pathology, King Hamad University Hospital, Al Sayh


Dyshormonogenetic goiter (DG) is the term given to the group of familial goiters owing to an inborn error of thyroid hormone metabolism. It is a benign, rare condition presenting architectural and cytological features that may lead to overdiagnosis of malignancy. Hence, in a patient with a history of hypothyroidism since infancy, a sense of apprehension is essential for a diagnosis of DG. We report a case of DG in a 12-year-old cretin girl.

How to cite this article:
Momin YA, H. Ansari SA. Dyshormonongenetic goiter: A rare and important entity.Arch Med Health Sci 2020;8:88-90

How to cite this URL:
Momin YA, H. Ansari SA. Dyshormonongenetic goiter: A rare and important entity. Arch Med Health Sci [serial online] 2020 [cited 2021 May 15 ];8:88-90
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Full Text


Dyshormonogenetic goiter (DG) previously named as congenital/familial goiter was described by Pendred in 1896 and Osler in 1897.[1] It is a rare entity with a prevalence of 30,000–50,000 live births and is the second most common cause (10%–15%) of permanent congenital hypothyroidism after thyroid dysgenesis.[1],[2],[3],[4] Inborn error of metabolism that interferes with biosynthesis of thyroid hormone leads to congenital hypothyroidism, wherein any one of multiple steps leading to thyroid hormone synthesis is defective: (1) iodide transport into thyrocytes, (2) iodide organification (binding to tyrosine residues – thyroglobulin [Tg]), and (3) iodide coupling to hormonally active T3–T4. DG is a less common cause of congenital hypothyroidism with mutations in thyroid peroxidase (TPO) gene.

 Case Report

A 12-year-old, mentally retarded child with a short stature presented with progressively enlarging neck swelling with dysphagia. Her birth history was unremarkable. However, she was a third child of a consanguineous marriage and was the only live child of her parents. She was illiterate and had coarse facial features, flattened palmar creases, and a protruded tongue. On examination, the thyroid was diffusely enlarged. Thyroid function tests were abnormal with markedly reduced T3, T4, and a raised thyroid-stimulating hormone (TSH). On ultrasound examination, the thyroid measured 11 cm × 10 cm × 5 cm was nodular with a solid and cystic component. She underwent subtotal thyroidectomy for pressure symptoms and to rule out malignancy. We received a thyroidectomy specimen. Grossly, the thyroid was enlarged and had a bosselated appearance, and cut section was nodular with multiple nodules of varying size [Figure 1]. Histological examination showed nodules separated by broad fibrous septa [Figure 2]a without normal thyroid tissue. Nodules showed follicular hyperplasia with macrofollicles and microfollicles with very little or marked absence of colloid [Figure 2]b. Alternating hypocellular edematous areas were seen as devoid of follicles. Follicular cells showed cytological atypia, increased nuclear–cytoplasmic ratio, and enlarged hyperchromatic nuclei, especially in internodular areas [Figure 3] and [Figure 4]. Focal areas showed oxyphilic cell change. A diagnosis of DG was rendered.{Figure 1}{Figure 2}{Figure 3}{Figure 4}


The underlying cause of inborn error of metabolism is a defect in the synthesis of thyroid hormone.[1],[2],[3],[4] This impaired synthesis leads to a loss of the negative feedback to the pituitary gland, which results in an overproduction of TSH and a compensatory goiter.[1],[2],[3],[4] The clinical presentation depends on the severity of the inborn error. A severe defect will lead to neonatal or congenital hypothyroidism, goiter, mental retardation, and growth abnormalities – cretinism. Milder defects will present later in life as goiter and minimal thyroid dysfunction – myxedema.[4],[5] Ultrasound reveals enlarged, orthotropic thyroid with solid hypoechoic nodules. Lobes develop a convex appearance laterally, and isthmus is readily visualized, in contrast to a normal gland. The thyroid gland size in children varies with age and should be correlated with height, weight, and body surface area.[6] Ultrasound scans at 20–22-week gestation are able to detect fetal thyroid hypertrophy.[7] Scintigraphy findings in patients having iodide-trapping defect, show no or very low radioiodine uptake in the thyroid; further, in contrast to athyreosis (absence of uptake), the salivary glands and the gastric mucosa lack uptake (”white scintigraphy”).[8],[9] In iodide organification defect (TPO and dual oxidase 2 [DUOX2]), radioiodine uptake is normal, but perchlorate discharge test is positive – most radioisotope is washed out into the bloodstream instead of accumulating in the thyroid.[8],[9] Patients with Tg and dehalogenase 1 defects show normal radioiodine uptake and normal perchlorate test.[8],[9] Macroscopically, the thyroid gland is enlarged and multinodular, and fibrous bands encapsulate individual nodules. Histologically, the process is diffuse, without normal thyroid tissue. There are marked follicular hyperplasia, hypercellularity, simple papillary formations, and decreased to absent colloid. The follicular cells typically exhibit severe cytologic atypia, including bizarre and markedly enlarged, hyperchromatic nuclei. These nuclear changes are most common in the internodular areas. The fibrosis entraps abnormal follicles, which can simulate a malignancy. Similar morphology was seen in our case. The presence in a thyroid gland of the combination of these morphologic features should suggest the diagnosis of DG. The only differential diagnosis is iatrogenic goiter due to the administration of antithyroidal agents. Our patient was cretin with no medication received till now. DG can mimic follicular carcinoma, papillary carcinoma, and Graves' disease, but strict histologic criteria will help separate these lesions. Treatment can be medical thyroid hormone replacement or surgical if there is symptomatic enlargement. Early treatment is particularly important in severe cases to avoid or diminish mental retardation and growth abnormalities. Our patient could have benefitted with medical line of treatment lest sought earlier medical attention. The prognosis is excellent with treatment.[1],[2],[3],[4],[5] Results after long-term follow-up have indicated satisfactory school performance, normal mean intelligence quotient values, and minimal motor dysfunction in treated children. However, specific defects in hearing-speech performance scales and minimal central nervous system deficits have been described.[5] Furthermore, T4 replacement therapy is given to normalize the serum TSH. Some disorders can be treated with iodine supplementation, for example, all SLC26A4, DUOX2, DUOXA2, and intrathyroidal iodine (IYD) defects and partial defects in SLC5A5.[10] Surgery is considered in patients with very large goiters (compressive or cosmetic reasons) or when malignancy is suspected. Fetal goiter detected by ultrasound with confirmed hypothyroidism (high amniotic TSH) can be treated by intra-amniotic injections of thyroxine.[11]


DG is considered as a form of thyroid hyperplasia due to enzymatic defects in hormone synthesis. Although DG being a benign entity, the architectural polymorphism and cellular atypia may mimic thyroid neoplasms and cause difficulties in diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's mother has given her consent for her child's images and other clinical information to be reported in the journal. The patient's mother understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


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