What is the cause of thyroid hemi‑agenesis and associated parathyroid agenesis in a patient without a history of neck surgery?

Thyroid Hemiagenesis and Parathyroid Agenesis: Congenital Developmental Anomaly

The absence of half the thyroid and parathyroid glands without prior surgery is caused by thyroid hemiagenesis (THA), a rare congenital disorder resulting from abnormal embryologic development during the first 5 weeks of gestation, with the parathyroid agenesis representing a separate but potentially associated developmental anomaly. 1

Embryologic Basis

THA occurs due to failure of thyroid lobe formation during embryogenesis, most likely from inadequate blood supply or maldevelopment of vessels at a very early developmental stage. 1 The key mechanisms include:

• The thyroid gland is the first endocrine organ to develop, with the thyroid anlage visible by day 20 post-conception 1
• Thyroid precursor cells proliferate from endodermal epithelium lining the primitive pharynx floor 1
• Inadequate blood supply leading to aplasia of one lobe appears to be a primary cause, as demonstrated by computed tomography angiography showing agenesis of the thyroid artery on the affected side 1
• The process of thyroid descent occurs asymmetrically, more to the left side, explaining why left-sided agenesis is far more common (80-87.5% of cases) 1

Parathyroid Involvement

The parathyroid glands develop from different embryologic pathways than the thyroid, so parathyroid agenesis is NOT automatically linked to ipsilateral thyroid hemiagenesis. 2 Important considerations:

• In documented cases of thyroid hemiagenesis with parathyroid pathology, parathyroid glands were found on the contralateral side to the thyroid agenesis in 3 of 9 cases 2
• When parathyroid glands are present, they are typically found in their usual anatomic positions despite the thyroid anomaly 3
• True parathyroid agenesis associated with thyroid hemiagenesis is extremely rare and would represent a separate congenital anomaly 2

Clinical Characteristics

Most patients with THA remain clinically euthyroid because the remaining lobe compensates through hypertrophy, though TSH and free T3 levels are typically higher than in normal populations. 1 Key features:

• Prevalence ranges from 0.05% to 0.5% in the general population 1
• Left lobe agenesis occurs in 80-87.5% of cases, with a left-to-right ratio of 4:1 1
• Right lobe agenesis is often associated with simultaneous isthmus absence 1
• The condition is usually discovered incidentally during imaging for other conditions 1

Diagnostic Approach

Diagnosis requires imaging confirmation, preferably combining thyroid ultrasonography with thyroid scintigraphy to distinguish true agenesis from other conditions. 1 The diagnostic algorithm:

• Ultrasonography is the gold standard for visualizing lobe absence and demonstrating the "hockey stick" appearance when isthmus is present 1
• Scintigraphy identifies functional tissue and can detect ectopic thyroid tissue not visible on ultrasound 1
• CT or MRI may incidentally detect the anomaly during evaluation of unrelated conditions 1
• Ultrasound alone can be misleading—scintigraphy distinguishes true agenesis from unilateral thyroiditis, infiltrative disease, or nonfunctional hypoplastic lobes 1

Associated Pathologies and Clinical Significance

Patients with THA have increased susceptibility to develop additional thyroid pathologies, likely due to chronic TSH elevation causing overstimulation of the remaining lobe. 1 Common associations:

• Thyroid pathologies: multinodular goiter, colloid goiter, follicular adenoma, Hashimoto thyroiditis, hypothyroidism, hyperthyroidism 4
• Extrathyroidal lesions reported include parathyroid adenoma or hyperplasia, cervical thymic cysts, ectopic sublingual thyroid, and thyroglossal duct cysts 4
• The frequency of thyroid abnormalities increases with age due to longer TSH exposure 4
• Congenital hypothyroidism occurs in 0.02% to 5.7% of children with THA, and THA accounts for 10.7% of congenital hyperthyrotropinemia cases 1

Management Recommendations

Systematic follow-up of all identified THA cases is recommended to detect concomitant disorders early, with consideration of L-thyroxine treatment to normalize TSH levels and potentially prevent associated thyroid pathologies. 1, 4 Management strategy:

• Increased vigilance with regular monitoring to reveal concomitant disorders as early as possible 1
• L-thyroxine treatment may theoretically benefit patients by lowering TSH to normal population levels, though evidence for preventing associated conditions is lacking 1
• No treatment is required if patients remain asymptomatic and euthyroid 5
• When parathyroid pathology is suspected in THA patients, standard parathyroid exploration should be performed bilaterally, as parathyroid glands can be found in usual locations regardless of thyroid anomaly 2, 3

Critical Pitfall

Do not assume ipsilateral parathyroid agenesis based solely on thyroid hemiagenesis—the embryologic pathways differ, and parathyroid glands develop independently from different pharyngeal pouches. 2, 3 If parathyroid disease is present, explore both sides of the neck following standard surgical recommendations.