Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

#Arrangoiz #ThyroidSurgeon #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #Hyperthyroidism #EndocrineSurgery #MountSinaiMedicalCenter #MSMC #Miami #Mexico #Florida #Doctor #Surgeon #Thyroid #ThyroidDisease

• Serum total T4 (TT4) and total T3 (TT3) concentrations:
  • Are a measure of both the bound and free hormone levels of these two hormones
• TT4 or TT3 levels should be interpreted in the context of the clinical situation:
  • Because many clinical conditions and medications alter the concentrations of thyroid hormone binding proteins and / or compete with the binding of thyroid hormones to the binding proteins:
    • As such, measured TT4 and TT3 levels may be affected, even though the bioactive free levels and thus, the thyroidal status, remain unchanged
• T3 is the active thyroid hormone:
  • It is primarily useful in the diagnosis and management of patients with hyperthyroidism
  • It occasionally can be used to differentiate stimulation induced thyrotoxicosis / Graves’ disease (TT3 / TT4 ratio > 20) from destruction induced thyrotoxicosis / subacute thyroiditis (TT3 / TT4 ratio < 12):
    • This assessment can be further augmented when TSH is considered as serum levels of TSH are generally suppressed in most untreated Graves’ patients, whereas they usually were not completely suppressed in patients with painless thyroiditis or subacute thyroiditis
  • Measurement of serum TT3 is not usually helpful if hypothyroidism is suspected:
    • Because the activity of 5’deiodinas type 2 enzyme (Dio2):
      • Which converts T4 to the biologically active T3:
        • Increases while serum T4 falls:
          • Thus maintaining normal T3 levels until the overall thyroid hormone levels are very low
• rT3, which may be elevated during nonthyroidal illness:
  • Is not biologically active:
    • As such, the utility of measuring it and other forms of inactive iodothyronine are limited during the evaluation of thyroid status
• Finally, the human anti-mouse antibodies (HAMAs) that interfere with TSH testing:
  • Can also interfere with the thyroid hormone assays
  • HAMA positivity:
    • May result in artificially elevated or reduced TT4, TT3, FT4, and FT3 levels
  • Patients who have received therapeutic monoclonal antibody treatment may be at increased risk of develop interfering positive HAMA titers

• Oral cavity SCC is staged using the AJCC 8th edition TNM system:
  • Which uniquely incorporates:
    • Depth of invasion (DOI) into the T classification and extranodal extension (ENE) into the N classification:
      • Two major changes from prior editions
• The following summarizes the complete staging system per the NCCN Head and Neck Cancer Guidelines
• Primary Tumor (T) Classification:
  • The T category is determined by both tumor size and DOI (measured from the basement membrane of adjacent normal mucosa, not tumor thickness):
    • Tis — Carcinoma in situ
    • T1 — Tumor ≤2 cm, DOI ≤5 mm
    • T2 — Tumor ≤2 cm with DOI >5 mm, OR tumor >2 cm and ≤4 cm with DOI ≤10 mm
    • T3 — Tumor >2 cm and ≤4 cm with DOI >10 mm, OR tumor >4 cm with DOI ≤10 mm
    • T4a — Tumor >4 cm with DOI >10 mm, OR invasion of adjacent structures (through cortical bone of mandible/maxilla, maxillary sinus, skin of face):
      • Superficial erosion of bone/tooth socket alone by a gingival primary does not qualify
    • T4b — Invasion of masticator space, pterygoid plates, skull base, and/or encasement of internal carotid artery
• Regional Lymph Nodes (N) — Clinical (cN):
  • N0 — No regional lymph node metastasis
  • N1 — Single ipsilateral node ≤3 cm, ENE(−)
  • N2a — Single ipsilateral node >3 cm but ≤6 cm, ENE(−)
  • N2b — Multiple ipsilateral nodes, none >6 cm, ENE(−)
  • N2c — Bilateral or contralateral nodes, none >6 cm, ENE(−)
  • N3a — Any node >6 cm, ENE(−)
  • N3b — Any node(s) with clinically overt ENE(+)
• Regional Lymph Nodes (N) — Pathological (pN):
  • The key difference from clinical N staging is that ENE now upstages nodal disease:
    • pN1 — Single ipsilateral node ≤3 cm, ENE(−)
    • pN2a — Single ipsilateral node ≤3 cm with ENE(+), OR single ipsilateral node >3–6 cm and ENE(−)
    • pN2b — Multiple ipsilateral nodes, none >6 cm, ENE(−)
    • pN2c — Bilateral/contralateral nodes, none >6 cm, ENE(−)
    • pN3a — Any node >6 cm, ENE(−)
    • pN3b — Single ipsilateral node >3 cm with ENE(+), OR multiple nodes any with ENE(+), OR single contralateral node of any size with ENE(+)
• Key Points on the 8th Edition Changes
  DOI vs. tumor thickness:
  • DOI is measured from the horizon of the basement membrane of adjacent uninvolved mucosa perpendicularly to the deepest point of invasion — distinct from tumor thickness, which is measured from the surface:
    • For every 5 mm increase in DOI, the T category increases by one level (cutoffs at 5 mm and 10 mm)
  • Upstaging impact:
    • Incorporation of DOI led to upstaging of approximately:
      • 29% to 36% of patients in the T category
    • ENE led to upstaging in:
      • ~13% for the N category
  • The 8th edition demonstrates improved prognostic discrimination compared to the 7th edition (Harrell’s C-index 0.70–0.74 vs. 0.65–0.69 for OS and DSS)
  • Clinical implications:
    • Patients with small tumors (formerly T1) upstaged to T3 based on DOI >10 mm may benefit from postoperative radiotherapy, even in the N0 setting
    • DOI is an independent predictor of regional nodal metastasis and disease-specific survival

The final 15-year analysis of the landmark SOFT and TEXT phase III trials provides the longest follow-up to date for endocrine therapy in premenopausal women with hormone receptor-positive early breast cancer.

These data reinforce that treatment intensity should be tailored according to recurrence risk. 

Key takeaways:

• Ovarian function suppression (OFS) significantly reduces breast cancer recurrence compared with tamoxifen alone.

• Exemestane + OFS provides the greatest reduction in recurrence and distant metastases, particularly in HER2-negative disease.

• The largest overall survival benefit was observed in high-risk patients, especially:

• Women < 35 years old
• High-grade tumors
• Patients requiring adjuvant chemotherapy

• For lower-risk patients who did not require chemotherapy, long-term survival remained excellent regardless of the endocrine regimen, emphasizing the importance of individualized treatment decisions.

Clinical Message

This landmark study confirms that not every premenopausal patient requires the same endocrine therapy. Careful risk stratification allows us to maximize oncologic outcomes while minimizing unnecessary toxicity. Personalized, multidisciplinary breast cancer care remains essential for achieving the best long-term results. 

Rodrigo Arrangoiz, MS, MD, FACS, FSSO
Breast Surgeon | Head & Neck Surgical Oncologist | Thyroid & Parathyroid Surgeon
Assistant Professor of Surgery, New York Medical College School of Medicine
Division of Surgical Oncology
Braman Comprehensive Cancer Center
Mount Sinai Medical Center – Miami, Florida

#BreastCancer #BreastSurgery #SurgicalOncology #BramanCancerCenter #MountSinaiMiami #HormonePositiveBreastCancer #PremenopausalBreastCancer #SOFTTrial #TEXTTrial #EvidenceBasedMedicine #CancerCare

👉The combination of 123I/99mTc-sestamibi subtraction planar pinhole scintigraphy with SPECT/CT and ultrasound improves the specificity of gland localization for minimally invasive parathyroidectomy.

👉https://doi.org/10.1016/j.amjsurg.2018.06.027

👉Rodrigo ARRANGOIZ MS, MD, FACS miembro de Sociedad Quirúrgica SC y pionero en MEXICO de la paratiroidectomia mínimamente invasiva radioguiada

👉For more information: http://www.hiperparatiroidismo.info

#Arrangoiz #ParathyroidExpert #ParathyroidSurgeon #Hiperparatiroidism #Hyperparathyroidism #Hipercalcemia #HeadandNeckSurgeon #MountSinaiMedicalCenter #MSMC #Miami #Mexico #Hiperparatiroidismo #ExpertoenParatiroides

Arrangoiz, R., Cordera, F. and Zambrano, M. (2026) Evidence-Based Approach to a “Missing” Parathyroid Gland during Thyroid or Parathyroid Surgery. International Journal of Otolaryngology and Head & Neck Surgery , 15, 261-283.

https://doi.org/10.4236/ijohns.2026.154024

Abstract

Failure to identify a parathyroid gland during thyroidectomy or parathyroidec-

tomy represents a well-recognized intraoperative challenge and is most com-

monly explained by ectopic gland location rather than true agenesis. A com-

prehensive understanding of parathyroid embryology, migration patterns, and

cervical anatomy is therefore essential for safe endocrine neck surgery and for

minimizing failed explorations, hypoparathyroidism, and recurrent disease.

This review provides a practical and surgically oriented overview of the “miss-

ing” parathyroid gland, integrating embryologic development, anatomic vari-

ability, operative identification strategies, and contemporary nomenclature sys-

tems. The embryologic descent of the superior and inferior parathyroid glands

from the fourth and third pharyngeal pouches, respectively, explains the pre-

dictable distribution of ectopic glands encountered during surgery. Superior

glands typically maintain relatively constant locations near the posterior as-

pect of the upper thyroid pole, whereas inferior glands demonstrate greater po-

sitional variability because of their longer migratory course with the thymus.

Common ectopic locations include the tracheoesophageal groove, retroesopha-

geal space, thyrothymic ligament, cervical thymus, carotid sheath, retropha-

ryngeal region, mediastinum, and intrathyroidal or subcapsular locations. This

review emphasizes operative pearls for gland identification, including recog-

nition of key landmarks such as the inferior thyroid artery, recurrent laryngeal

nerve, prevertebral fascia, cervical thymus, and characteristic parathyroid fat

pads. Strategies for systematic exploration are discussed in the context of both

thyroidectomy and parathyroidectomy. Additionally, the manuscript reviews

the Perrier classification system for ectopic parathyroid glands and proposes

DOI: 10.4236/ijohns.2026.154024 Jul. 9, 2026 261 Int’l J. of Otolaryngology and Head & Neck SurgeryR. Arrangoiz et al.

its practical application during cervical exploration to facilitate structured lo-

calization of missing glands. By combining embryologic principles with oper-

ative anatomy and contemporary surgical nomenclature, this review aims to

provide endocrine surgeons, trainees, and head and neck surgeons with a clin-

ically relevant framework for identifying orthotopic and ectopic parathyroid

glands, reducing operative failure, and improving surgical outcomes in thy-

roid and parathyroid surgery.

Keywords

Parathyroid Gland, Ectopic Parathyroid Gland, Missing Parathyroid Gland,

Parathyroid Embryology, Thyroidectomy, Parathyroidectomy, Mediastinal

Parathyroid Gland, Intrathyroidal Parathyroid Gland, Perrier Classification,

Surgical Anatomy, Parathyroid Localization

#Arrangoiz #ThyroidSurgeon #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #Hyperthyroidism #EndocrineSurgery #MountSinaiMedicalCenter #MSMC #Miami #Mexico #Florida #Doctor #Surgeon #Thyroid #ThyroidDisease

• Pretibial myxedema occurs in 0.5% to 4.3% of patients with Graves’ disease:
  • It is an infiltrative dermopathy:
    • Most often involving the skin of the legs
  • It is manifested by painful, pruritic, raised plaque-like violaceous and hyperpigmented lesions:
    • That have the texture of an orange peel
• Acropachy occurs in less than 1% of patients with Graves’ disease:
  • It is manifested by clubbing and periosteal new bone formation of the metacarpal bones and the phalanges

#Arrangoiz #ThyroidSurgeon #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #Hyperthyroidism #EndocrineSurgery #MountSinaiMedicalCenter #MSMC #Miami #Mexico #Florida #Doctor #Surgeon #Thyroid #ThyroidDisease