Diagnostic Thyroid Testing: Serum Thyroglobulin

  • Thyroglobulin (Tg):
    • Is a large glycoprotein that is stored as colloid:
      • The primary storage form of thyroid hormone, in the lumen of thyroid follicles
    • It is continuously secreted into circulation from the thyroid gland:
      • Thereby reflecting the mass of normal and malignant thyroid tissue
  • Higher serum concentrations result from:
    • TSH stimulation and / or injury of thyroid tissue:
      • However, for the individual with an intact thyroid gland:
        • Its clinical value for evaluating thyroid dysfunction or goiter is limited in the era of modern serum thyroid function testing and imaging
        • However, the demonstration of a suppressed serum Tg level in such a patient can be useful in differentiating factitious thyrotoxicosis (from exogenous thyroid hormone ingestion) from excessive endogenous thyroid hormone release of any etiology:
          • In this situation, when thyrotoxicosis is due to ingestion of exogenous thyroid hormone:
            • Normal thyroid hormone production is suppressed and serum Tg levels are decreased
          • In contrast, if excess thyroid hormone is produced from the thyroid:
            • Serum Tg levels are elevated
  • In current clinical practice:
    • The primary use of serum Tg concentrations is as a tumor marker in patients with differentiated thyroid cancer:
      • That is obtained to detect persistent and / or recurrent disease after a total thyroidectomy and radioactive iodine (131I) ablation
  • Most Tg assays have only first-generation functional sensitivity between 0.5 and 1 ng/mL:
    • But the second generation Tg assays are rapidly becoming the standard and have an improved functional sensitivity of 0.05 to 0.1 ng/mL
  • The Tg assay can be made more sensitive to detect persistent or recurrent tumor:
    • After stimulation by TSH:
      • Either endogenously by withholding thyroxine treatment in an athyreotic patient or with administration of recombinant human TSH (rhTSH):
        • The latter of which results in an approximate tenfold increase in basal serum Tg concentrations
  • Detection of persistent and / or recurrent disease in thyroid cancer depends on the performance of Tg immunometric assays:
    • Which currently have suboptimal sensitivity and high interassay variability
  • Virtually all immunometric methods:
    • Will report an undetectable Tg level in euthyroid Tg Ab positive controls:
      • Approximately 25% of patients with differentiated thyroid cancer have a positive serum TgAb titer:
        • Thus when a suspicious lymph node or neck mass is detected in an individual who has undergone a total thyroidectomy:
          • An unmeasurable basal or rhTSH-stimulated Tg in the setting of a positive serum TgAb level:
            • Does not necessarily exclude thyroid cancer recurrence
        • It is reasonable in this relatively uncommon situation to measure Tg instead by Tg Ab-resistant radioimmunoassay (RIA) or liquid chromatography tandem mass spectrometry:
          • Which are available at some specialty endocrine laboratories.
  • When the serum Tg Ab titer is positive:
    • It may also be used as a surrogate marker of tumor persistence / recurrence
  • In one study, a > 50% decrease of Tg Ab levels within the first year after a total thyroidectomy:
    • Was associated with the absence of tumor recurrence / persistence in all patients studied
    • Tumor recurrence / persistence was present in 37% of patients who had any rise of serum Tg Ab within the same period
  • Thus thyroid cancer patients with rising Tg antibody levels:
    • Are at high risk for disease persistence / recurrence and should be evaluated promptly
    • In addition, the sensitivities and absolute values reported by different methods of measuring Tg and TgAb are highly variable:
      • It is essential to always use the same Tg and TgAb method when following an individual over time for tumor persistence/recurrence
  • Finally, the presence of interfering heterophile antibodies (antibodies against the animal-derived antibodies used in the immunometric assay):
    • May rarely result in abnormally high or low serum Tg levels
    • The most common interfering antibodies are HAMAs:
      • Clinically, this should be suspected when an elevated serum Tg level is inappropriate for the clinical situation and does not increase with rhTSH stimulation
      • When heterophile antibody is suspected, the clinician should repeat the test using a commercially available heterophile-blocking tube (HBT) or measure Tg with an RIA assay

Subareolar Abscesses

  • Subareolar abscesses:
    • Are a common type of nonlactational abscess
  • The pathophysiology:
    • Is believed to be keratin plugging of the lactiferous ducts:
      • Resulting in squamous metaplasia
    • The periductal inflammation that results can progress to abscess formation
  • A nipple cleft is an anatomic variant that seems to be associated with the condition:
    • Also known as Zuska’s disease
  • Because of their chronic nature including the formation of fistulas:
    • Their management involves different considerations than the management of lactational abscesses
  • Aspiration:
    • Is an appropriate practice for initial management of small non-loculated lactational and nonlactational abscesses
  • When aspiration is possible:
    • More invasive and painful procedures such as incision and drainage with postoperative daily wound packing are less appropriate as an initial step:
      • However, an abscess managed with aspiration may require serial procedures
  • Data from several small studies have demonstrated that:
    • Between 37% and 60% of abscesses will require more than one aspiration procedure
  • Aspiration is less likely to be successful for:
    • Larger abscesses
    • Multiloculated abscesses
    • Abscesses with a delay in presentation greater than 6 days
  • Antibiotics:
    • Should always be prescribed, and the likelihood of MRSA should be taken into account when choosing an initial antibiotic until culture results are available
    • Recurrent subareolar abscesses:
      • May also require anaerobic antibiotic coverage
        • For example, trimethoprim-sulfamethoxazole prescribed with metronidazole may be a good initial choice
    • Only a minority of abscesses are treated successfully with antibiotics alone without a drainage procedures
  • Surgical excision of a chronic subareolar abscess cavity:
    • May be indicated to prevent repeated episodes and there has been debate over the most appropriate specific technique
    • Removal of the terminal ducts appears to be an important step in decreasing recurrences
    • Therefore, procedures that remove only the abscess cavity but do not remove these ducts and the fistula tract will be less successful
    • Radial elliptical incision of the involved ductal tissue and fistula tract, including excision of the central nipple, so as to include the nipple cleft in the excision, has been shown to have a high rate of success
    • Removal of the terminal ducts through a periareolar incision, also called Hadfield’s procedure, has had a higher recurrence rate in small case studies
    • Ultrasound-guided percutaneous needle electrolysis causing tissue ablation within the fistula is an experimental procedure
  • Smoking is a risk factor for development of subareolar abscesses, and smoking cessation should be encouraged:
    • However, smoking is not a contraindication to surgery and should not be a barrier to proceeding
  • References
    • Snider HC. Management of mastitis, abscess, and fistula. Surg Clin North Am. 2022;102(6):1103-1116. doi:10.1016/j.suc.2022.06.007
    • Lam E, Chan T, Wiseman SM. Breast abscess: evidence based management recommendations. Expert Rev Anti Infect Ther. 2014;12(7):753-762. doi:10.1586/14787210.2014.913982
    • Barron AU, Luk S, Phelan HA, Williams BH. Do acute-care surgeons follow best practices for breast abscess management? A single-institution analysis of 325 consecutive cases. Journal of Surgical Research. 2017;216:169-171. doi:https://doi.org/10.1016/j.jss.2017.05.013
    • Naeem M, Rahimnajjad MK, Rahimnajjad NA, Ahmed QJ, Fazel PA, Owais M. Comparison of incision and drainage against needle aspiration for the treatment of breast abscess. Am Surg. 2012;78(11):1224-7. 
    • David M, Handa P, Castaldi M. Predictors of outcomes in managing breast abscesses-a large retrospective single-center analysis. Breast J. 2018;24(5):755-763. doi:10.1111/tbj.13053