Pregnancy complicated by fetal goiter in a post-pituitary adenectomy patient: a case description

Introduction

Fetal goiter is a rare condition with a complex and multifactorial etiology, involving maternal thyroid dysfunction, genetic susceptibility, and fetal thyroid hormone (TH) synthesis abnormalities. Its estimated incidence ranges from 0.002% to 0.006% (1). With the widespread use of high-resolution prenatal ultrasonography, the prenatal diagnosis rate of fetal goiter has significantly improved. Functional assessment and morphological monitoring can effectively reduce the risk of long-term complications (2). This article presents a case of fetal goiter with multiple anomalies in a pregnant woman with post-pituitary adenectomy hypothyroidism, and explores the underlying pathological mechanisms and the ultrasonographic implications.

Case presentation

All the procedures in this study were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and the Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient for the publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

A 23-year-old female patient, with no history of smoking, alcohol consumption, or drug allergies, underwent craniotomy for resection of a pituitary tumor 6 months prior to the pregnancy. Postoperative diagnosis confirmed hypothyroidism, for which she had irregularly taken levothyroxine sodium tablets. Her recent thyroid function test results were as follows: free triiodothyronine (FT3): 1.2 nmol/L (reference range, 2.3–4.2 nmol/L), free thyroxine (FT4): 5.4 nmol/L (reference range, 10.3–24.5 nmol/L), and thyroid stimulating hormone (TSH) 18.34 mU/L (reference range, 0.27–4.2 mU/L). Six months after the operation, the patient developed symptoms of abdominal distension, and ultrasound examination revealed that she was 23 weeks pregnant with a fetus with multiple congenital anomalies, prompting her referral to Gansu Provincial Maternity and Child-care Hospital.

Ultrasonography at our institution revealed the following: Bilateral lateral ventriculomegaly, with a left ventricular width of 47 mm and a right ventricular width of 23 mm (Figure 1A), and a “dumbbell-shaped” moderately echogenic mass (26 mm × 15 mm) anterior to the fetal trachea, encircling the airway with homogeneous internal echogenicity. Color Doppler flow imaging showed no significant vascularity in the central portion of the mass but sparse flow signals peripherally (Figure 1B-1D, and Videos 1,2). Three-dimensional surface rendering confirmed anterior cervical swelling (Figure 1E), a narrowed fetal thoracic cage (transverse thoracic diameter: 48 mm) with an increased cardiothoracic ratio (cardiac transverse diameter: 32 mm), and a ventricular septal defect (2.5 mm) (Figure 1F). Persistently extended upper limbs and a fixed cross-legged lower limb posture without dynamic changes were also observed (Figure 2A,2B and Video 3). The metatarsal bones were poorly visualized, with only phalanges identified in both feet (Figure 2C,2D, and Video 4). The amniotic fluid assessment showed a maximum vertical pocket depth of 106 mm and an amniotic fluid index of 368 mm. The ultrasonographic diagnosis was as follows: (I) severe fetal hydrocephalus; (II) an anterior cervical hyperechoic mass, suggestive of thyroid goiter; (III) a narrowed thoracic cage with increased cardiothoracic ratio and ventricular septal defect; (IV) metatarsal hypoplasia and fixed limb postures; and (V) moderate polyhydramnios. Prenatal umbilical vein puncture confirmed fetal hypothyroidism (TSH: 11.32 mU/L; normal range, 0.38–4.34). The family opted to terminate the pregnancy at an external institution, as in addition to the fetal malformation, the patient was unmarried, and the pregnancy unplanned. Documentation provided by the family indicated that the autopsy findings were consistent with our ultrasound diagnoses, though post-procedure images were unavailable.

Figure 1 Prenatal ultrasound image of fetus. (A) Two-dimensional axial view of the fetal head showed bilateral lateral ventricular dilatation, more pronounced in the left side (as indicated by the white arrow). (B) Two-dimensional longitudinal section of the neck revealed an enlarged thyroid gland exhibiting a “dumbbell” morphology (as indicated by the white arrow). (C) Two-dimensional longitudinal and transverse sections of the neck further delineated the enlarged thyroid gland (as indicated by the white arrow). (D) Color Doppler imaging showed sparse peripheral blood flow signals within the enlarged thyroid gland (as indicated by the white arrow). (E) Three-dimensional volume-rendered imaging revealed anterior cervical swelling in the fetal neck region (as indicated by the white arrow). (F) Four-chamber view of the fetal heart showed a ventricular septal defect (as indicated by the yellow arrow).

Figure 2 Prenatal ultrasound image of fetus. (A) Three-dimensional volume-rendered imaging showed the fetal hands in an extended position in utero (as indicated by the white arrows). (B) Three-dimensional volume-rendered imaging showed the fetal lower limbs in a cross-legged posture in utero (as indicated by the white arrow). (C) Two-dimensional imaging revealed indistinct visualization of the left fetal metatarsal bones, with only phalanges identifiable (as indicated by the white arrow). (D) Three-dimensional volume-rendered imaging further confirmed poor delineation of the left fetal metatarsal bones, showing phalangeal structures exclusively (as indicated by the white arrow).

Discussion

Fetal goiter is often the primary manifestation of fetal thyroid abnormalities (3). Possible pathogenic mechanisms include maternal Graves’ disease or thyroid dysfunction, maternal use of antithyroid drugs during pregnancy, maternal iodine deficiency, congenital defects in TH synthesis, and chromosomal or genetic abnormalities (1). In this case, the patient developed hypopituitarism following pituitary adenoma resection, leading to dysfunction of the hypothalamic-pituitary-thyroid axis (4). This type of hypothyroidism, caused by insufficient TSH secretion from the pituitary gland, is termed “central hypothyroidism” (or “secondary hypothyroidism”). Although the patient intermittently took antithyroid medications postoperatively, her TH levels remained sub-optimally controlled. This inadequate hormonal regulation ultimately resulted in fetal thyroid dysfunction and the associated congenital malformations.

The gold standard for diagnosing fetal goiter is umbilical cord blood thyroid function testing. However, as umbilical vein puncture is an invasive procedure carrying risks of hemorrhage, intrauterine infection, preterm labor, and fetal demise, prenatal ultrasound has emerged as the most direct and crucial imaging modality for identifying fetal goiter (5). Sonographic characteristics of fetal goiter include a symmetrical midline or paramedian neck mass demonstrating “dumbbell-shaped” or “butterfly-shaped” morphology encircling the trachea, with a thyroid transverse diameter/neck circumference ratio >0.16; Simple goiters typically exhibit a homogeneous isoechoic or hypoechoic internal texture, while complex goiters may demonstrate cystic degeneration (15%), calcifications (5%), or fibrosis. Indirect sonographic signs include polyhydramnios secondary to tracheal compression, reduced fetal movements, and fetal growth restriction (6). Thyroid vascular distribution is correlated with functional status. Hyperthyroid states manifest with central gland hypervascularity [resistance index (RI) <0.6], while hypothyroid states display either normal vascularity or marked reduction compared to hyperthyroid conditions, characterized by peripheral vascular paucity or absence (a RI >0.8 serves as a sensitive discriminant) (3). Studies have shown that the downregulation of vascular endothelial growth factor expression leads to reduced microvascular density, which constitutes the core mechanism underlying diminished blood flow (7,8).

Isolated fetal goiter accounts for 60–70% of all cases, and is not generally associated with other structural anomalies. Over 95% of affected infants achieve normal neurodevelopmental outcomes with timely intervention (9). Conversely, fetal goiter with concomitant structural malformations occurs in approximately 30–40% of cases, with common associated anomalies including hydrocephalus (35%), cardiac anomalies (25%), skeletal dysplasia (20%), and polyhydramnios (50%) (2,6). Compared to isolated cases, these cases have worse prognoses, with survival rates of around 60–70% and a 2–3-fold increased risk of neurodevelopmental impairments (10). In the present case, the fetus exhibited thyroid enlargement accompanied by multiple structural malformations.

The fetal thyroid initiates TH secretion and synthesis at 12 weeks of gestation. During early pregnancy, fetal cerebral and somatic development is entirely dependent on maternal TH supply (11). Early gestational TH deficiency disrupts multiple ion transport functions, resulting in excessive cerebrospinal fluid (CSF) production. Concurrently, impaired CSF reabsorption by arachnoid granulations due to TH insufficiency exacerbates fluid accumulation (12). In this case, the severe fetal hydrocephalus likely resulted from TH deficiency-induced dual mechanisms: increased CSF production, and a diminished absorption capacity. Nehrer et al. proposed that THs directly regulate chondrocytes and osteoblasts, promoting their proliferation, differentiation, and apoptosis to orchestrate bone remodeling (13). Consequently, fetal hypothyroidism typically manifests as delayed skeletal maturation, growth retardation, and skeletal dysplasia (14). The observed thoracic hypoplasia and bilateral metatarsal hypoplasia in this fetus might have been pathophysiologically linked to these mechanisms. Increased cardiothoracic ratios and ventricular septal defects likely stem from TH deficiency-mediated impairments in cardiomyocyte proliferation/differentiation, extracellular matrix remodeling, and cardiac hemodynamics, ultimately leading to cardiac enlargement and structural defects (15). Notably, the persistent fixed fetal position observed during serial ultrasonographic evaluations aligns with the characteristic sonographic sign of reduced fetal movements associated with hypothyroid states.

Emerging evidence indicates (16) that approximately 15–20% of congenital hypothyroidism cases are associated with genetic mutations, with currently known pathogenic variants involving ten genes: NIS/SLC5A5 (sodium-iodide symporter), PDS/SLC26A4 (pendrin), TPO (thyroid peroxidase), TG (thyroglobulin), DUOX2 (dual oxidase 2), DUOXA2 (dual oxidase maturation factor 2), DUOX1 (dual oxidase 1), DUOXA1 (dual oxidase maturation factor 1), IYD/DEHAL1 (iodotyrosine deiodinase), and SLC26A7 (solute carrier family 26 member 7). However, genetic testing was not performed in this case due to maternal-related constraints. Further, studies have indicated that in cases of maternal euthyroidism with fetal goiter, the positive genetic screening rate reaches 35%, underscoring the clinical necessity for comprehensive evaluation of both maternal and genetic factors. Early diagnosis of fetal hypothyroidism is critical, as over 90% of infants with congenital hypothyroidism achieve normal neurodevelopment and intellectual capacity when treated either prenatally or within 2 weeks postpartum. Conversely, delayed intervention leads to irreversible parenchymal neurological damage, predisposing infants to long-term developmental deficits in auditory, linguistic, spatial cognition, and psychological domains (17). These findings emphasize the substantial clinical value of timely prenatal diagnosis and therapeutic intervention.

Prenatal sonographic differentiation of fetal goiter requires distinction from the following pathologies: (I) congenital cervical lymphangioma, which presents as multilocular cystic structures typically located in the lateral neck region, lacking solid thyroid tissue components; (II) cervical teratoma, which usually appears as a heterogeneous mass in the lateral neck, demonstrating well-demarcated boundaries from thyroid tissue, with potential inclusions of calcifications and adipose components; (III) cervical hemangioma, which may present as solid or mixed echogenicity masses (some cases can cause tracheal compression similar to goiter, exhibiting marked vascularity on Doppler imaging); and (IV) cervical neurogenic tumors, which present as solid masses with non-thyroid origins, often located in the lateral/posterior neck, and may display calcifications or infiltrative growth into surrounding tissues (18).

Fetal goiter with multiple malformations represents a complex pathological process arising from the interplay of hypothalamic-pituitary-thyroid axis dysfunction and genetic determinants. Prenatal ultrasound, through comprehensive morphological and hemodynamic evaluation, provides critical evidence for early diagnosis and clinical intervention. This case, characterized by adverse pregnancy outcomes due to suboptimal maternal thyroid function management following pituitary surgery, underscores the clinical imperative of enhancing thyroid surveillance in post-pituitary adenectomy patients and implementing standardized management protocols during pregnancy.

Acknowledgments

None.

Footnote

Funding: This work was supported by the Science and Technology Program of Gansu Province (No. 23JRRA1383).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1027/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was provided by the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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