Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Study Overview:
  • Author:
    • Anita K. Lam et al., Hong Kong cohort published in Cancer, 2005
  • Design:
    • Retrospective cohort of patients with thyroid carcinoma managed postoperatively:
      • From 2000 to 2003
  • Population:
    • Patients who underwent total thyroidectomy, categorized by RAI administration (yes / no) and lymph node metastasis characteristics
  • Primary Outcome:
    • Lymph node (regional) recurrence-free survival
• Key Findings
  • RAI vs No‑RAI:
    • RAI-treated patients with lymph node metastases (N1) had significantly lower rates of regional lymph node recurrence compared to those managed without RAI
• Influencing Factors:
  • Higher node burden (N1b vs N1a) and presence of microscopic extrathyroidal extension increased recurrence risk
• Multivariate Analysis:
  • RAI independently predicted improved lymph node recurrence-free survival, even after adjusting for patient age, number of involved nodes, and ETE
• Clinical Implications for Expert Surgeons:
  • Strengthens rationale for recommending RAI in patients with clinical / pathologic nodal metastases, particularly those with multiple nodes or N1b disease:
    • Supports adjuvant RAI as an effective tool to reduce surgical re-treatment for nodal recurrence
  • Highlights the importance of comprehensive nodal assessment in postoperative planning to determine RAI need
  • Encourages a risk-adapted approach:
    • For example, reserving RAI for patients with ≥ 1 cm nodal involvement or aggressive features
• Summary:
  • Lam AK and colleagues provide more evidence supporting the benefit of RAI in reducing regional lymph node recurrence in node-positive thyroid cancer patients, particularly those with more extensive nodal disease
  • This data reinforces a targeted use of RAI in intermediate-risk cohorts to optimize outcomes
• Reference:
  • Lam AK, et al. RAI impact on lymph node recurrence: Hong Kong cohort study. Cancer. 2005;103(5):920–9. Summary for expert thyroid surgeons

Trabajo realizado por Rodrigo Arrangoiz MS, MD, FACS y el equipo de Sociedad Quirúrgica S.C. que se presento en Septiembre del 2018 en el 6th World Congress of the International Federation of Head and Neck Oncology Societies llevado acabo en Buenos Aires, Argentina.

Rodrigo Arrangoiz is a board-certified surgical oncologist who subspecializes in breast cancer and head and neck cancer. Dr. Arrangoiz earned his medical degree at the Anahuac University Medical School in Mexico City, Mexico and graduated Suma Cum Laude. He completed his internship and residency in general surgery at Michigan State University, where he was named chief resident during his fifth year of residency. Dr. Arrangoiz also completed a complex surgical oncology, head and neck fellowship at the Fox Chase Cancer Center in Philadelphia and at the same time he undertook a master’s in science (Clinical Research for Health Care Professionals) at Drexel University in Philadelphia. Dr. Arrangoiz also participated in a two-year global online fellowship in head and neck surgery and oncology through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center.

Dr. Arrangoiz has participated in multiple courses and academic congresses as a lecturer and guest professor and has also participated in several publications on topics related to his specialty that include oral cavity cancer, hyperparathyroidism, thyroid cancer, breast cancer, endocrine tumors, squamous cell carcinoma of the head and neck, and more. He is board certified by the American Board of Surgery, the Mexican Board of General Surgery and the Mexican Board of Oncology.

He is a member of various medical associations such as the American College of Surgeons, American Thyroid Association, American Head and Neck Society, American Medical Association, American Society of Clinical Oncology, Association of Academic Surgeons, Society of Surgical Oncology, The Society of Surgery of the Alimentary Tract, Society of American Gastrointestinal Endoscopic Surgeons, and the American Society of Breast Surgeons, among others.

Specialty:

Head and Neck Surgery
Thyroid and Parathyroid Surgery
Breast Surgery
Complex Surgical Oncology

Areas of Clinical Interest:

Malignant thyroid disease (papillary, follicular, medullary, anaplastic thyroid cancer, thyroid lymphoma, and metastatic disease to the thyroid gland) benign thyroid diseases (goiter, multinodular goiter, substernal goiter, hyperthyroidism), hyperparathyroidism / hypercalcemia, benign and malignant breast diseases, head and neck surgery and head and neck cancer.

Click to access is-breast-cancer-associated-with-primary-hyperparathyroidism-324.pdf

👉Without surgery, primary hyperparathyroidism results in decreased bone density in the majority of patients, raising questions regarding how long patients should be followed without intervention.

#CheckYourCalcium #Arrangoiz #ParathyroidSurgeon #ParathyroidExpert #MountSinaiMedicalCenter #MSMC #Miami #Mexico #EndocrineSurgery #SurgicalOncologist #HeadandNeckSurgeon

• Study Overview:
  • Citation:
    • Haymart MR, Banerjee M, Stewart AK, Koenig RJ, Birkmeyer JD, Griggs JJ. Use of radioactive iodine for thyroid cancer. JAMA. 2011;306(7):721–728. 
  • Type:
    • Observational cohort using the National Cancer Database (NCDB) and SEER registries from 2004 to 2008
  • Population:
    • 189,219 adult patients with well-differentiated thyroid cancer (papillary or follicular) who underwent total thyroidectomy at 981 U.S. cancer centers
  • Objectives:
    • Analyze trends in RAI usage from 1990 to 2008
    • Identify patient-, tumor-, and hospital-level predictors of RAI administration
    • Assess variation in use across centers, adjusted for disease severity
• Key Findings:
  • Rising Use Over Time
  • RAI utilization increased significantly across all tumor sizes between 1990 and 2008
  • Variation Driven by Non-Clinical Factors
  • Patient / tumor characteristics explained ~21% of variation in RAI use
  • Hospital traits (type, volume) accounted for ~17%, and 29% remained unexplained, suggesting practice pattern influence
• Disease Stage and Use:
  • Compared to Stage IV:
    • Patients with Stage I disease were much less likely to receive RAI (OR 0.34), but Stage II / III use was similar to Stage IV (OR ~1)
• Regional Disparities:
  • Rate of RAI use for low-, medium-, and high-risk disease varied by region (49% to 66%):
    • Indicating inconsistency in treatment approaches 
• Clinical Implications:
  • Overuse concern:
    • Increasing RAI use even in low-risk settings raises questions about overtreatment
  • Practice patterns matter:
    • Institutional priorities and physician preferences strongly influenced whether patients received RAI, beyond tumor biology
  • Guideline alignment needed:
    • The lack of deficit-stage conformity highlights a need to standardize RAI delivery based on risk stratification, not provider bias
  • Takeaway for Expert Surgeons:
    • Recognize that RAI is often employed inconsistently, even for Stage II to III disease, despite limited evidence of benefit in these groups
    • Encourage benchmarking and quality initiatives within institutions to ensure RAI administration aligns with ATA risk-based guidelines
    • Educate multidisciplinary teams that evidence-based risk stratification should dictate RAI use, minimizing unnecessary exposure for patients with lower-stage disease

• Study Design and Methods:
  • Type:
    • Retrospective cohort of 469 consecutive ATA low / intermediate-risk DTC patients:
      • From 2009 to 2015
  • Groups:
    • RAI-treated:
      • 328 (69.9%)
    • No-RAI:
      • 141 (30.1%)
  • Primary Outcome:
    • Composite biochemical or structural recurrence at median 17.5 months
  • Adjustment Method:
    • Inverse-Probability Weighted Regression Adjustment (IPWRA):
      • To control for selection bias and baseline confounders
• Key Results:
  • Overall recurrence rates:
    • RAI group:
      • 9.6% (95% CI 6.3–12.9%)
    • No-RAI group:
      • 15.9% (95% CI 11.1–20.7%)
  • Relative Risk Reduction:
    • 42% lower recurrence with RAI:
      • RR = 0.58; 95% CI 0.35–0.91; p = 0.018
  • Recurrence risk factors (multivariable analysis):
    • pN1 disease:
      • OR 4.07
    • Male sex:
      • OR 2.71
    • Larger tumor size:
      • OR 1.03 per mm
    • Microscopic ETE:
      • OR 2.36
  • Subgroup benefit:
    • Greatest in patients with ≥ 2 intermediate-risk factors:
      • pN1
      • mETE
• Clinical Implications for Surgeons:
  • In intermediate-risk patients with multiple adverse features:
    • RAI appears to significantly reduce recurrence
  • Risk features amplifying benefit include:
    • Clinical / pathologic lymph node metastasis (pN1)
    • Microscopic ETE
    • Larger primary tumors
    • Male gender
  • Absolute recurrence reduction:
    • ~ 6.3% in this cohort:
      • Notable for patient counseling
• Surgical Considerations:
  • Multifactor intermediate-risk disease:
    • Should prompt strong consideration for adjuvant RAI
  • Younger patients, low-risk burden (e.g., single small node, no ETE):
    • May still be appropriate for surveillance
  • Shared decision-making critical:
    • Discuss ~ 6% absolute benefit balanced against RAI side effects
  • RAI dose and prep:
    • Not specified in the study; current practice supports 60 to 100 mCi with rhTSH preparation
• In summary:
  • Prete et al. provide robust level III evidence that RAI reduces recurrence in intermediate-risk DTC patients with multiple adverse factors
  • This supports a nuanced, risk-adapted recommendation for RAI use in your multidisciplinary practice
• Reference:
  • Prete A, et al. Benefit of RAI in intermediate-risk DTC patients with multiple features. Endocrine. 2024;84(1):123–131.

• Four-Gland Hyperplasia (Four Abnormal Glands):
  • Hyperplasia of all four glands may be seen as:
    • Primary hyperparathyroidism (HPT)
    • Progressive secondary HPT
    • Tertiary HPT
• If multi-gland disease (MGD) in primary HPT is known preoperatively:
  • Genetic testing should be considered prior to operation:
    • As this may further change the operative approach
• There are two distinct operative approaches in MGD:
  • Total parathyroidectomy with auto-transplantation (TP)
  • Sub-total parathyroidectomy (STP):
    • In a sub-total parathyroidectomy, the most normal appearing gland is chosen to be the remnant (ideally an inferior gland):
      • Which is then cut back to approximately the size of a normal gland
    • The gland is subsequently tagged with a Prolene suture:
      • Cut 1 to 2 cm long with a Hemoclip on the ends:
        • Which will aid in identification should re-exploration be required
    • Care should be taken not to compromise the vascular supply of the gland with this suture

• Each approach carries different risks, benefits, and indications, as shown in the Table:
  • Which should always be considered with regard to the patient and his or her underlying pathology (e.g., genetic syndrome, tertiary HPT)

• Other important considerations when dealing with MGD include:
  • Cervical thymectomy:
    • Due to the increased risk of ectopic supernumerary glands in MGD
  • Cryo-preservation of resected tissue:
    • Should be performed to protect against the rare, though devastating, complication of permanent hypoparathyroidism due to graft or remnant failure
  • If available, iPTH can be used to help guide the extent of resection in sub-total:
    • Aiming for a greater than 90% reduction at the completion of the operation
  • Close observation postoperatively for hypoparathyroidism and hungry bone syndrome regardless of approach

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• Patients with PHPT have some degree of renal dysfunction or symptoms:
  • In approximately 80% of the cases of PHPT
• The renal manifestations implicated with PHPT are:
  • Decreased glomerular filtration rate
  • Hypercalciuria
  • Nephrolithiasis
  • Nephrocalcinosis
  • Impaired urinary concentrating ability:
    • Sometimes leading to:
      • Polyuria
      • Polydipsia
      • Nocturia
  • Reduced fractional phosphate reabsorption:
    • Leading to hypophosphatemia
  • Increased urinary exertion of magnesium
• Nephrolithiasis:
  • Was previously reported in approximately 40% to 80% of patients:
    • But now occur only in about 20% to 25% of the cases
  • The pathophysiology is thought to be related to:
    • The filtered load of calcium in the glomerulus:
      • That increases proportionately with the degree of hypercalcemia
  • Most renal stones in patients with PHPT:
    • Are composed of calcium oxalate:
      • Although slightly alkaline urine:
        • May favor the precipitation of calcium phosphate stones
  • Stone formers are more likely to be hypercalciuric:
    • But less than one-third of the hypercalciuric patients with PHPT:
      • Actually develop renal stones
  • Hypercalciuria:
    • Is not a predictor of nephrolithiasis in patients with PHPT:
      • Is no longer considered as an indication for surgery
• Nephrocalcinosis:
  • Which refers to renal parenchymal calcification:
    • Is found in less than five percent of patients:
      • Is more likely to lead to renal dysfunction
• The incidence of hypertension is variable;
  • Anywhere between 30% to 50% of patients with PHPT
• Hypertension:
  • Appears to be more common in older patients
  • Correlates with the magnitude of renal dysfunction
  • In contrast to other symptoms:
    • Is least likely to improve after parathyroidectomy
• Another plausible explanation of the origin of hypertension in patients with PHPT:
  • Is the synthesis of parathyroid hypertensive factor:
    • That triggers an increase in blood pressure
• The elevated levels of PTH is also linked with the disruption in the:
  • Renin-angiotensin- aldosterone system 

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• Study Overview:
  • Design:
    • Prospective, long-term study combining two RCTs conducted at a single center in Gliwice, Poland
  • Participants:
    • Low-risk group (n = 277):
      • Received 30, 60, or 100 mCi RAI
    • Intermediate-risk group (n = 46):
      • Randomized to 60 mCi (n = 20) vs 100 mCi (n = 26)
    • Follow-up duration:
      • Mean ~ 11 years (range 3 to 19 years) 
• Key Findings:
  • Low-Risk Patients:
    • Excellent response rates:
      • 88% (30 mCi), 89% (60 mCi), 90% (100 mCi)
    • Incomplete structural response:
      • ~ 1% to 1.6%
    • Indeterminate response:
      • ~ 9%
  • Long-term outcomes were comparable across all doses:
    • Confirming adequacy of lower doses in low-risk cases
• Intermediate-Risk Patients:
  • Excellent response (after first ablation):
    • 85% in both 60 mCi and 100 mCi groups 
  • Indeterminate response:
    • 6.5%
  • Incomplete structural response:
    • 6.5%
  • Incomplete biochemical response:
    • 2.2% (only in 100 mCi group)
• Cumulative excellent response:
  • 72% after possible additional therapies
  • 11% of patients required further RAI
  • 4.3% required treatment for recurrence 
  • No significant differences were observed between the two dose levels in final therapeutic outcomes
• Conclusions:
  • Low-Risk:
    • All three RAI doses 30, 60, and 100 mCi:
      • Achieve similar long-term disease response:
        • Supports use of lower-dose ablation
  • Intermediate‑Risk:
    • 60 mCi RAI appears sufficient:
      • No additional benefit shown with 100 mCi:
        • Based on long-term structural and biochemical outcomes
• Clinical implication:
  • In intermediate-risk DTC:
    • A moderate 60 mCi RAI dose is a safe and effective option with favorable long-term results
• Clinical Take‑Home:
  • Tailored approach:
    • For intermediate-risk patients, standardizing to 60 mCi avoids higher-dose exposure without compromising efficacy
    • Supports ATA and ETA guidance favoring risk-adapted dosing strategies:
      • Minimizes overtreatment while optimizing outcomes
• Reference:
  • Kukulska et al. Arch Med Sci. 2022;18(5):1241–1247.

• While all patients with symptomatic primary hyperparathyroidism (PHPT) should consider surgery (95% of patients are usually symptomatic when appropriate history is taken):
  • It is also indicated in some asymptomatic patients (5% of the cases of PHPT):
    • Indications:
      • Age less than 50
      • Kidney disease:
        • GFR less than 60
      • Osteoporosis
      • Serum calcium greater than 1 mg/dl above normal
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393490/

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• In primary hyperparathyroidism due to adenomas:
  • The normal feedback on parathyroid hormone production by extracellular calcium seems to be lost:
    • Resulting in a change in the set point
• In primary hyperparathyroidism from parathyroid hyperplasia:
  • An increase in the cell numbers is probably the cause of the change in the set point
• The chronic excessive resorption of calcium from bone caused by excessive parathyroid hormone can result in:
  • Osteopenia
  • In severe cases, this may result in osteitis fibrosa cystica:
    • Which is characterized by subperiosteal resorption of the distal phalanges, tapering of the distal clavicles, salt-and-pepper appearance of the skull, and brown tumors of the long bones
      • This is not commonly seen now
• In addition, the chronically increased excretion of calcium in the urine:
  • Can predispose to the formation of renal stones
• The other symptoms of hyperparathyroidism:
  • Are due to the hypercalcemia itself:
    • And are not specific to hyperparathyroidism
  • These can include:
    • Muscle weakness
    • Fatigue
    • Volume depletion
    • Nausea and vomiting
    • In severe cases, coma and death
  • Neuropsychiatric manifestations are particularly common and may include:
    • Depression
    • Confusion
    • Subtle deficits that are often characterized poorly and may not be noted by the patient (or may be attributed to aging)
  • Increased calcium can increase gastric acid secretion, and persons with hyperparathyroidism:
    • May have a higher prevalence of peptic ulcer disease
  • Rare cases of pancreatitis have also been attributed to hypercalcemia
• A prospective cohort study by Ejlsmark-Svensson et al:
  • Reported that in patients with primary hyperparathyroidism, quality-of-life questionnaire scores were significantly lower:
    • In association with moderate-severe hypercalcemia:
      • Than in relation to mild hypercalcemia:
        • However, quality of life did not seem to be related to the presence of organ-related manifestations of primary hyperparathyroidism, such as osteoporosis, renal calcifications, and renal function impairment
        • This suggests that hypercalcemia is the primary driver of an impaired quality of life

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