Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• 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/

#Arrangoiz #ParathyroidSurgeon #ParathyroidExpert #Hyperparathyroidism #PrimaryHyperparathyroidism #CancerSurgeon #EndocrineSurgery #Teacher #Surgeon #HeadandNeckSurgeon #SurgicalOncologist #ParathyroidAdenoma #Hypercalcemia #ElevatedCalciumLevels #Miami #MountSinaiMedicalCenter #MSMC #Mexico #Hialeah

👉The overproduction of parathyroid hormone (PTH), termed hyperparathyroidism (HPT), can be categorized as primary, secondary, or tertiary.

👉Primary hyperparathyroidism (PHPT) arises from an unregulated overproduction of PTH from an abnormal parathyroid gland.

👉Increased PTH levels may also occur as a compensatory response to hypocalcemic states resulting from chronic renal failure or gastrointestinal (GI) malabsorption of calcium. This secondary HPT can be reversed by correction of the underlying problem (e.g., kidney transplantation for chronic renal failure).

👉However, chronically stimulated parathyroid glands may occasionally become autonomous, resulting in persistence or recurrence of the hypercalcemia after successful renal transplantation, resulting in tertiary HPT. This review paper will focus on PHTP

#Arrangoiz #ParathyroidSurgeon #ParathyroidExpert #Hyperparathyroidism #EndocrineSurgery #Hypercalcemia #MountSinaiMedicalCenter #MSMC #Miami #Mexico

Follow-Up After Curative Treatment for Stage I–III Breast Cancer

The 2026 ASCO guideline emphasizes risk-adapted survivorship care while reaffirming that routine imaging and laboratory testing to detect distant recurrence do not improve survival in asymptomatic patients.

1. History and Physical Examination

Clinical follow-up should be individualized according to recurrence risk, treatment received, patient preferences, and survivorship needs.

Recommended schedule:

• Years 1–3: Every 3–6 months
• Years 4–5: Every 6–12 months
• After 5 years: Annually

Each visit should include:

• Interval history
• Breast/chest wall examination
• Regional lymph node examination
• Evaluation for signs or symptoms of recurrence
• Assessment of treatment-related toxicities (lymphedema, neuropathy, menopausal symptoms, cardiotoxicity, bone health)
• Review of endocrine therapy adherence when applicable
• Counseling regarding healthy lifestyle, exercise, weight management, alcohol moderation, and smoking cessation

Virtual follow-up visits may be appropriate for selected patients.

2. Breast Imaging

After Breast-Conserving Surgery

• First mammogram 6–12 months after completion of radiation therapy (or approximately 1 year after the preoperative mammogram if radiation is omitted).
• Annual mammography thereafter.

After Unilateral Mastectomy

• Annual mammography of the contralateral breast.

After Bilateral Mastectomy

• Routine mammography is not recommended.

3. Breast MRI

Routine MRI surveillance is not recommended.

MRI should be reserved for patients who meet established high-risk screening criteria, including:

• BRCA1 or BRCA2 mutation
• TP53 or PALB2 mutation
• Lifetime breast cancer risk ≥20–25%
• Selected patients with very dense breasts and high genetic risk

4. Imaging for Distant Recurrence

Routine imaging is not recommended in asymptomatic patients.

Do not routinely obtain:

• CT scans
• PET/CT
• Bone scan
• Liver ultrasound
• Chest radiograph
• Brain MRI

These studies should only be performed when symptoms, physical examination, or laboratory findings suggest recurrence.

5. Laboratory Testing

Routine laboratory surveillance is not recommended.

Do not routinely obtain:

• Complete blood count (CBC)
• Comprehensive metabolic panel (CMP)
• Liver function tests
• Alkaline phosphatase

unless clinically indicated.

6. Tumor Markers

Routine measurement of serum tumor markers is not recommended.

Do not routinely obtain:

• CA 15-3
• CA 27.29
• CEA

in asymptomatic patients.

7. Circulating Tumor DNA (ctDNA)

Routine surveillance with circulating tumor DNA (ctDNA) is not recommended outside of clinical trials, as current evidence has not demonstrated an improvement in survival or quality of life when molecular recurrence is detected before clinical recurrence.

8. Survivorship Care

Survivorship visits should include:

• Management of endocrine therapy adherence
• Assessment of long-term toxicities
• Lymphedema screening
• Bone health assessment
• Cardiovascular risk reduction
• Exercise counseling
• Weight management
• Smoking cessation
• Alcohol moderation
• Psychosocial support
• Sexual health counseling
• Coordination with the primary care physician

Key Recommendations

• History and physical examination: Every 3–6 months for years 1–3, every 6–12 months for years 4–5, then annually.
• Annual mammography remains the only recommended routine surveillance imaging.
• Routine CT, PET/CT, bone scan, MRI, ultrasound, or chest X-ray are not recommended in asymptomatic patients.
• Routine CBC, chemistry panels, liver function tests, and tumor markers (CA 15-3, CA 27.29, CEA) are not recommended.
• Routine ctDNA surveillance is not recommended outside clinical trials.
• Follow-up should be individualized according to recurrence risk and survivorship needs, with increasing emphasis on healthy lifestyle interventions and management of treatment-related toxicities.

Reference:
Runowicz CD, et al. ASCO Guideline Update: Breast Cancer Follow-Up and Management After Primary Treatment. Journal of Clinical Oncology. 2026.

• Differential Diagnosis of Hypercalcemia:Primary hyperparathyroidism:Solitary adenoma:85% to 90% of the cases
  • • Multigland Disease:Multigland hyperplasia:3% of the cases
      • Doble adenoma:6% to 9% of the cases
      • Triple adenoma:0.3% of the cases
  • Secondary hyperparathyroidism
  • Tertiary hyperparathyroidism
  • Familial hypocalciuric hypercalcemia
  • Medications:
    • Lithium
    • Hydrochlorothiazide
  • Malignancy:
    • Parathyroid carcinoma
    • Multiple myeloma
    • Tumors producing PTH-related peptide:Ovarian cancer
      • Lung cancer
    • Acute or chronic leukemia
  • Granulomatous diseases:
    • Sarcoidosis, histioplasmosis, tuberculosis
  • Thyrotoxicosis
  • Paget disease
  • Increased intake:
    • Milk-alkali syndrome
    • Vitamin A toxicity
    • Vitamin D toxicity

• Primary hyperparathyroidism (PHPT):Is caused by an inappropriate, autonomous  secretion of parathyroid hormone (PTH) by the parathyroid gland(s):Which leads to an elevated serum calcium concentration or wide variations of the serum calcium concentration
  • Single gland disease:Caused by a single, enlarged, overactive gland, is found in 85% to 90% of cases
  • Multiple gland disease occurs in 10% to 15% of the cases:Multiple gland disease may consist of:Double adenomas (6% to 9% of the cases)
    • • Four-gland hyperplasia (3% of the cases)
      • Three enlarged and one normal appearing gland (0.3% of the cases).Because asymmetric hyperplasia is common, it is difficult to distinguish between multiple adenomas and hyperplasia and the term multiple gland disease is preferred
  • PHPT in the United States usually presents quite early:Often when hypercalcemia is noted during routine laboratory testing
  • Signs may include:Nephrolithiasis, decreased bone density, and fragility fractures, and subjective symptoms may include fatigue, cognitive changes, depression, constipation and other gastrointestinal complaints, musculoskeletal pain, nocturia, and rarely pruritus:Many patients may appear asymptomatic:A detailed history often uncovers symptoms:95% of the cases have symptoms when appropriate history is taken:The recently revised guidelines for asymptomatic PHPT include a more extensive evaluation of the skeletal and renal systems
  • A family history of endocrine disorders should be investigated:As hyperparathyroidism alone can be familial or can present as a component of multiple endocrine neoplasia (MEN) types 1 and 2A

Medullary Thyroid Cancer (MTC) accounts for 1% to 2% of thyroid cancers in the United States.

• MTC is different from other types of thyroid cancers (which are derived from thyroid follicular cells – the cells that make thyroid hormone), because it originates from the parafollicular C cells (also called “C cells”) of the thyroid gland. These cells do not make thyroid hormone and instead make a different hormone called calcitonin.

MTC can, and frequently does, spread to lymph nodes and can also spread to other organs.

MTC is likely to run in families (inherited forms) in up to 25% of diagnoses, and inherited forms can be associated with other endocrine tumors, in syndromes called Multiple Endocrine Neoplasia (MEN) 2A and MEN 2B.

• In addition to MTC, patients with MEN2A may have tumors of the adrenal glands called pheochromocytomas or in the parathyroid glands (parathyroid adenomas). Patients with MEN2B, have MTC, pheochromocytomas and neuromas (typically a benign growth or tumor of nerve tissue) in the lining of the mouth and/ or gastrointestinal track.
• Patients with an inherited form of MTC usually have a mutation in a gene called the RET proto-oncogene. This mutation is present in all of the cells in their body (a germline mutation) and these mutations cause the development of MTC. This is important because in family members of a person with an inherited form of MTC, a blood test for a mutation in the RET protooncogene can lead to an early diagnosis of MTC and, to curative surgery to remove it. However, in the majority of patients (~ 75%) a germline mutation is not found – indicating that MTC is not an inherited or inheritable condition. In these cases, MTC is called sporadic.

Whether MTC is sporadic or familial can be determined by a blood test for the RET protooncogene. Anyone diagnosed with MTC should have this test run to determine whether the MTC is familial (meaning other family members may also have MTC that has not yet been diagnosed) or sporadic.

What are the Symptoms of Medullary Thyroid Cancer?

Medullary thyroid cancer usually presents as a lump or nodule in the thyroid. It may be noted by the patient or discovered during routine neck examination by the doctor. Sometimes, the nodule is discovered incidentally by imaging studies done for other unrelated reasons (CT of the neck, PET scan, or carotid ultrasound). The nodule may cause no symptoms, but in some cases the tumor may have spread to lymph nodes in the neck, which may be enlarged on physical examination.

Patients with advanced MTC may complain of pain in the neck, jaw, or ear. If a nodule is large enough to compress the windpipe or the esophagus, it may cause difficulty with breathing or swallowing. Hoarseness can be present if the cancer invades the nerve that controls the vocal cords.

MTC is usually more aggressive than the other more common types of thyroid cancer, and it is usually easier to treat and control if it is found before it spreads to lymph nodes in the neck or other parts of the body.

Thyroid function tests such as TSH are usually normal, even when MTC is present.

If you have a family history of MTC and have tested positive for the RET mutation, then you should see an endocrinologist to help determine how best to follow you or treat you.

How is Medullary Thyroid Cancer Diagnosed?

A diagnosis of thyroid cancer is usually made by a fine needle aspiration (FNA) biopsy of a thyroid nodule, or after the nodule is surgically removed. Patients in whom the results of an FNA biopsy (or histopathology) are suggestive or indicative of MTC should be further evaluated with measurement of the proteins calcitonin and carcinoembryonic antigen (CEA) in the blood, which are typically elevated in patients with MTC. These tests are useful to confirm the diagnosis of MTC which can help ensure the surgeon plans the correct surgery, and also serve as tumor markers during long-term follow-up to detect any remaining disease or recurrence of the cancer.

What is a RET Mutation?

The RET proto-oncogene is located on chromosome 10. A genetic mutation in the RET oncogene is seen in all cells in the body in patients with the hereditary forms of MTC. Mutations in RET can also be seen only in the tumor cells in patients with sporadic MTC. Since the discovery of the RET oncogene, more than 100 different mutations have been identified in the gene in patients with MTC.

Genetic counseling and testing for RET gene mutations should be offered to patients diagnosed with MTC and first-degree relatives (parents, siblings and children of someone diagnosed with MTC) of all patients with proven germline mutations (hereditary MTC). If close relatives, especially children, are found to have the RET mutation on a blood test, the thyroid gland can be removed before MTC has a chance to develop or at least in its very early stages.

How is Medullary Thyroid Cancer Treated?

The primary treatment for MTC is surgery, and the currently accepted approach is to remove the entire thyroid gland (total thyroidectomy) (See thyroid surgery brochure). Often patients with MTC will have thyroid cancer present in the lymph nodes of the neck or upper chest. These lymph nodes are usually removed at the time of thyroid surgery or sometimes, at a later surgery if found subsequently. After surgery, patients need to take thyroid hormone replacement medication for life.

Unlike papillary and follicular thyroid cancer, medullary thyroid cancer does not take up iodine, and consequently radioactive iodine treatment is not a treatment option for patients with MTC.

Patients with MTC with very high levels of calcitonin should have imaging prior to surgery to determine whether the tumor has spread to sites outside the thyroid and/or outside the neck. If there is evidence of cancer outside the neck, surgery may be more palliative, aimed at reducing local complications caused by the tumor, rather than completely eliminating all tumor. Other treatment options (external beam radiation, or chemotherapy) may need to be used together with surgery after careful discussion with the patient.

New chemotherapeutic agents that have shown promise treating other advanced cancers are increasingly available for treatment of thyroid cancers. Two such agents, Vandetanib and Cabozantinib have been FDA approved for use by patients with MTC. These drugs do not cure advanced cancers that have spread widely throughout the body, but they can often slow down or partially reverse the growth of the cancer. These treatments are usually given by an oncologist (cancer specialist) and require care at specialized medical centers.

What is the Follow-Up of Patients with Medullary Thyroid Carcinoma?

Periodic follow-up examinations are essential for all patients with MTC because the thyroid cancer can return, sometimes many years after successful initial treatment. These follow-up visits include a careful history and physical examination, with particular attention to the neck area. Neck ultrasound is also a very important tool to visualize the neck and look for nodules, lumps or enlarged lymph nodes that might indicate that the cancer has recurred.

Blood tests are also important in the follow-up of MTC patients. All patients who have had their thyroid glands removed require thyroid hormone replacement with levothyroxine. Thyroid stimulating hormone (TSH) should be checked periodically, and the dose of levothyroxine adjusted to keep TSH in the normal range. There is no need to keep TSH suppressed in patients with MTC.

Measurement of calcitonin and CEA are a necessary routine part of the follow-up of patients with MTC. Following thyroidectomy, it is hoped that calcitonin levels will be essentially undetectable for life. A detectable or rising calcitonin level should raise suspicion for possible cancer recurrence. Detectable calcitonin levels may require additional tests.

Rodrigo Arrangoiz MS, MD, FACS

• He is an expert in the management medullary thyroid carcinoma.

• Articles published on MTC:

  • https://www.gavinpublishers.com/articles/Review-Article/Journal-of-Clinical-Endocrinology-and-Diabetes/Medullary-Thyroid-Carcinoma-Literature-Review-and-Current-Management

  • http://www.remedypublications.com/american-journal-of-otolaryngology-and-head-and-neck-surgery/articles/pdfs_folder/ajohns-v1-id1026.pdf

Training:

• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

#Arrangoiz

#Teacher

#Surgeon

#Cirujano

#SurgicalOncologist

#CirujanoOncologo

#CancerSurgeon

#CirujanodeCancer

#HeadandNeckSurgeon

#CirugiaEndocrina

#EndocrineSurgery

#CirujanodeCabezayCuello

• It is a surgical sub-specialty that deals mainly with benign and malignant tumors of the head and neck region, including:
  • The scalp, facial region, eyes, ears, nose, nasal fossae, paranasal sinuses, oral cavity, pharynx (nasopharynx, oropharynx, hypopharynx), larynx (supraglotic larynx, glottis larynx, subglotic larynx), thyroid gland, parathyroid gland, salivary glands (parotid glands, submandibular glands, sublingual glands, minor salivary glands), soft tissues of the neck, skin of the head and neck region.
• The head and neck surgeon’s work area:
  • Does not cover tumors or diseases of the brain and other areas of the central nervous system or those of the cervical spine:
    • This is the neurosurgeon field
• Among the diagnostic procedures performed by the head and neck surgeon, are the following:
  • Nasopharyngolaryngoscopy:
    • Performed to examine, evaluate and, possibly perform a biopsy, of oral cavity, pharyngeal and laryngeal lesions
• The surgeries most commonly performed by the head and neck surgeon are:
  • Total or near total thyroidectomies
  • Hemithryoidectomies (lobectomies)
  • Comprehensive neck dissections
  • Selective neck dissections
  • Maxillectomies:
    • Total maxillectomy
    • Subtotal maxillectomy
    • Infrastructure maxillectomy
    • Suprastructure maxillectomy
    • Medial maxillectomy
  • Mandibulectomy:
    • Segmental
    • Marginal
  • Tracheostomy
  • Salivary gland surgeries:
    • Parotid gland operations:
      • Limited superficial parotidectomy with identification and preservation of the facial nerve
      • Superficial parotidectomy with identification and preservation of the facial nerve
      • Near total parotidectomy with identification and preservation of the facial nerve
      • Total parotidectomy
    • Submandibular gland resection
    • Sublingual gland resection
  • Resection of tumors of the oral cavity:
    • Glossectomy
    • Resection of the floor of the mouth tumors
  • Resection of tumors of the pharynx
  • Resection of tumors of the larynx
  • Split-thickness skin grafts
  • Full-thickness skin grafts
  • Sentinel lymph node mapping and sentinel lymph node biopsy
  • Resection of malignant skin tumors (BCC, SCC, melanoma) of the head and neck region
• The training of the head and neck surgeon includes mastering the following subjects:
  • Surgical Anatomy
  • History and Basic Principles of Head and Neck Surgery
  • Epidemiology, Etiology, and Pathology of Head and Neck Diseases
  • Diagnostic Radiology of the Head and Neck Region
  • Tumors of the Scalp, Skin and Melanoma
  • Eyelids and Orbit
  • Nasal Cavity and Paranasal Sinuses
  • Skull Base and Temporal Bone
  • Lips and Oral Cavity
  • Pharynx and Esophagus
  • Larynx and Trachea
  • Cervical Lymph Nodes
  • Thyroid and Parathyroid Glands
  • Salivary Glands
  • Neurogenic Tumors and Paragangliomas
  • Soft Tissue Tumors
  • Bone Tumors and Odontogenic Lesions
  • Reconstructive Surgery
  • Oncologic Dentistry and Maxillofacial Prosthetics
  • Principles of Radiation Oncology
  • Principles of Chemotherapy
  • Molecular Oncology, Genomics and Immunology
  • Nutrition
  • Biostatistic

My name is Rodrigo Arrangoiz I am a board-certified surgical oncologist who sub-specializes in breast cancer and head and neck cancer. I earned his medical degree at the Anahuac University Medical School in Mexico City, Mexico and graduated Suma Cum Laude. I completed his internship and residency in general surgery at Michigan State University, where he was named chief resident during his fifth year of residency. I 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. I 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.

I have 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. I am board certified by the American Board of Surgery, the Mexican Board of General Surgery and the Mexican Board of Oncology.

I am 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, among others.

https://www.msmc.com/doctor/rodrigo-arrangoiz/

#Arrangoiz #HeadandNeckSurgeon #CancerSurgeon #SurgicalOncologist #MountSinaiMedicalCenter #MSMC #Mexico #Miami #ThyroidSurgeon #ParathyroidSurgeon

• The natural history of a non-toxic multi nodular goiter (MNG):
  • Involves variable growth of individual nodules:
    • This may progress to hemorrhage and degeneration:
      • Followed by:
        • Healing and fibrosis
    • Calcification:
      • May be found in areas of previous hemorrhage
  • Some nodules may develop autonomous function:
    • Autonomous hyperactivity:
      • Is conferred by somatic mutations of thyrotropin or thyroid-stimulating hormone receptor (TSHR):
        • In 20% to 80% of toxic adenomas and some nodules of MNGs
      • Autonomously functioning nodules:
        • May become toxic in 10% of patients
      • Hyperthyroidism predominantly occurs:
        • When single autonomous nodules are larger than 2.5 cm in diameter:
          • However, in geographic areas with iodine deficiency, smaller autonomous nodules:
            • May produce systemic, clinical manifestations of hyperthyroidism
  • The development of hyperthyroidism in MNG takes many years:
    • The process evolves from:
      • A small gland with one small nodule or more to nodules increasing progressively in number, size, and function
    • Initially, most patients are euthyroid:
      • But with enlarging goiters, autonomy develops:
        • Illustrated by low or suppressed serum thyroid-stimulating hormone (TSH) with normal serum levels of thyroid hormones
• Graves’ disease:
  • Is a syndrome that consists of:
    • Hyperthyroidism
    • Goiter
    • Ophthalmopathy (orbitopathy)
    • Occasionally a dermopathy referred to as:
      • Pretibial or localized myxedema
  • Hyperthyroidism:
    • Is the most common feature of Graves’ disease:
      • Affecting nearly all patients
    • It is caused by autoantibodies to the TSHR (TSHR-Ab):
      • That activate the receptor:
        • Thereby stimulating thyroid hormone synthesis and secretion:
          • As well as thyroid growth:
            • Causing a diffuse goiter
  • The histology of the thyroid gland in patients with Graves’ hyperthyroidism:
    • Is characterized by:
      • Follicular hyperplasia
      • A patchy (multifocal) lymphocytic infiltration
      • Rare lymphoid germinal centers:
        • The majority of intra-thyroidal lymphocytes are:
          • T cells:
            • Germinal centers (B cells) are much less common than in chronic autoimmune thyroiditis (Hashimoto’s disease)
      • Thyroid epithelial cell size:
        • Correlates with the intensity of the lymphocytic infiltrate:
          • Suggesting thyroid cell stimulation by local B cells secreting TSHR-Ab
    • The presence of TSHR-Ab antibodies:
      • Is positively correlated with:
        • Active disease and with relapse of the disease
  • There is an underlying genetic predisposition:
    • Because of an increased frequency of haplotypes human leukocyte antigen:
      • HLA-B8 and HLA-DRw3 in white patients
      • HLA-Bw36 in Japanese patients
      • HLA-Bw46 in Chinese patients
    • However, it is not clear what triggers the acute episodes:
      • Some factors that may incite the immune response are:
        • Pregnancy:
          • Particularly the postpartum period
        • Iodine excess:
          • Particularly in geographic areas of iodine deficiency
      • Lithium therapy
      • Viral or bacterial infections
      • Glucocorticoid withdrawal
  • The etiology and pathogenesis of Graves’ ophthalmopathy are not known:
    • It may involve cytotoxic lymphocytes and cytotoxic antibodies:
      • Sensitized to a common antigen found in:
        • Orbital fibroblasts, orbital muscle, and thyroid tissue:
          • Which may cause inflammation:
            • Resulting in proptosis of the globes
    • It has been suggested recently that TSHR-bearing circulating fibroblasts and fibrocytes:
      • May be activated directly by the TSHR-Ab
  • The pathogenesis of dermopathy may also involve this mechanism:
    • Patients with exophthalmos and particularly those with dermopathy:
      • Almost always have high titers of circulating TSHR autoantibodies:
        • Suggesting that these two clinical manifestations represent the most severe form of this disease

#Arrangoiz #CancerSurgeon #ThyroidSurgeon #ParathyroidSurgeon #HeadandNeckSurgeon #ThyroidExpert #SurgicalOncologist #EndocrineSurgery #MountSinaiMedicalCenter #Miami #ThyroidNodule #ToxicNodularGoiter #TNG #MultinodularGoiter #GravesDisease #Hyperthyroidism #Goiter

• Definition of problem:
  • Primary hyperparathyroidism (PHPT):
    • Is the unregulated overproduction of parathyroid hormone (PTH) resulting in abnormal calcium homeostasis
• Frequency:
  • Primary hyperparathyroidism is more common in women:
    • The incidence being:
      • 66 per 100,000 person-years in females
      • 25 per 100,000 person-years in males
  • In a large study of 3.5 million enrollees in Kaiser Permanente of Southern California:
    • The incidence fluctuated over time but was not seen to decrease substantially​
    • On the contrary, the prevalence of primary hyperparathyroidism saw a substantial increase in this population
  • The mean age at diagnosis has remained between:
    • 52 and 56 years
• Etiology:
  • In approximately 85% to 90% of cases:
    • Primary hyperparathyroidism is caused by:
      • A single adenoma
  • In 15% of cases:
    • Multiple glands are involved:
      • Multiple adenomas:
        • Doble adenomas
        • Triple adenomas
      • Hyperplasia (4 glands)
  • Rarely, primary hyperparathyroidism is caused by parathyroid carcinoma
  • The etiology of adenomas or hyperplasia:
    • Remains unknown in most cases
  • Familial cases can occur as either part of the:
    • Multiple endocrine neoplasia syndromes (MEN 1 or MEN 2a)
    • Hyperparathyroid-jaw tumor (HPT-JT) syndrome
    • Familial isolated hyperparathyroidism (FIHPT)
    • Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism also belong to this category
  • The molecular genetic basis of MEN 1 (Wermer Syndrome):
    • Is an inactivating mutation of the MEN1 gene:
      • Located on chromosome band 11q13
  • MEN 2a is caused by a:
    • Germline mutation of the Ret proto-oncogene on chromosome 10. 
  • Germline mutation of HRPT2 localized on chromosome arm 1q:
    • Is responsible for HPT-JT
• While FIHPT is genetically heterogeneous

#Arrangoiz #ParathyroidSurgeon #ParathyroidSurgeon #HeadandNeckSurgeon #EndocrineSurgery #Hyperparathyroidism #MSMC #MountSinaiMedicalCenter #Mexico #Miami

• Incidence:
  • The incidence of PHPT has remained relatively stable in the last couple of decades
  • PHPT is more common in women than in men:
    • Two to three times higher in incidence rate in women
  • PHPT is more common in the elderly population:
    • The incidence increases with age
    • The incidence starts to increase at age 50:
      • 1 in 500 postmenopausal women will have PHPT
      • 1 in 1000 men over 50 will have PHPT
  • Incidence rates in the USA:
    • 60 cases per 100, 000 women
    • 20 cases per 100,000 men
• Prevalence
  • In the USA:
    • 1% of the postmenopausal female population will have PHPT
  • International prevalence rates:
    • 3% of the postmenopausal female population will have PHPT
  • The prevalence PHPT has risen in the last couple of decades:
    • From 1995 and 2010 it has tripled:
      • Women:
        • 76 to 233 cases per 100,000 women
      • Men:
        • 30 to 85 cases per 100,000 men
  • Gender:
    • African Americans have the highest prevalence of PHPT:
      • Followed by caucasians followed by Asians
    • Hispanics have a lower prevalence rate
  • Reason for the higher prevalence compared to incidence in PHPT:
    • Is that only 20% to 25% of patients with PHPT in the USA will end up having surgery
    • Only 50% of patients in the USA with nephrolithiasis and PHPT have surgery
    • Only 20% of patients with osteoporosis and PHPT in the USA go onto have surgery
    • The probability of having surgery decreases with age:
      • The older one gets the less likely they will be offered an intervention
• Genetics of PHPT:
  • Six primary conditions associated with an inherited predisposition for the development of PHPT:
    • MEN Type 1:
      • Incidence:
  • The incidence of PHPT has remained relatively stable in the last couple of decades
  • PHPT is more common in women than in men:
    • Two to three times higher in incidence rate in women
  • PHPT is more common in the elderly population:
    • The incidence increases with age
    • The incidence starts to increase at age 50:
      • 1 in 500 postmenopausal women will have PHPT
      • 1 in 1000 men over 50 will have PHPT
  • Incidence rates in the USA:
    • 60 cases per 100, 000 women
    • 20 cases per 100,000 men
• Prevalence
  • In the USA:
    • 1% of the postmenopausal female population will have PHPT
  • International prevalence rates:
    • 3% of the postmenopausal female population will have PHPT
  • The prevalence PHPT has risen in the last couple of decades:
    • From 1995 and 2010 it has tripled:
      • Women:
        • 76 to 233 cases per 100,000 women
      • Men:
        • 30 to 85 cases per 100,000 men
  • Gender:
    • African Americans have the highest prevalence of PHPT:
      • Followed by caucasians followed by Asians
    • Hispanics have a lower prevalence rate
  • Reason for the higher prevalence compared to incidence in PHPT:
    • Is that only 20% to 25% of patients with PHPT in the USA will end up having surgery
    • Only 50% of patients in the USA with nephrolithiasis and PHPT have surgery
    • Only 20% of patients with osteoporosis and PHPT in the USA go onto have surgery
    • The probability of having surgery decreases with age:
      • The older one gets the less likely they will be offered an intervention
• Genetics of PHPT:
  • Only 5% to 10% of patients with PHPT will with have an underlying genetic predisposition
  • Six primary conditions associated with an inherited predisposition for the development of PHPT:
    • MEN Type 1:
      • Pituitary Tumors
      • PHPT:
        • Has almost 100% penetrance
        • It is the first endocrine disease to manifest
        • It manifests at a young age
      • Pancreatic neuroendocrine tumors:
        • Duodenal and gastronomes
      • Foregut carcinoid tumors:
        • Lung
        • Thymus
      • Adrenal adenomas
    • MEN Type 2A:
      • Medullary thyroid carcinoma:
        • 100% penetrance
        • First endocrinopathy to manifest
      • Pheochromocytoma
      • PHPT:
        • Only 20% to 30% develop PHPT
        • Will depend on the RET mutation (codon)
        • They develop mild hypercalcemia
        • More common to see multi gland disease but you can also get one gland disease
        • Age of onset is younger:
          • Two decades earlier than sporadic PTHP
    • MEN Type IV:
      • Phenotypically similar to MEN type 1
      • Mutation CDKNIB gene
    • Hyperparathyroidism jaw tumor syndrome (rare):
      • Ossifying fibromas
      • Mixture of renal tumors, uterine fibroids
    • Familial hypocalciuric hypercalcemia (FHH – predisposes to hypercalcemia):
      • FHH is mainly classified into three different types depending on the genetic cause
      • FHH type 1:
        • Is the most common type of FHH and is caused by changes (also known as pathogenic variants or mutations) in the CASR gene
        • The protein made from the CaSR gene:
          • The calcium-sensing receptor (CaSR protein), monitors and regulates the level of calcium in the blood
      • FHH type 2:
        • Is caused by changes in the GNA11 gene
      • FHH type 3:
        • Is caused by changes in the AP2S1 gene
      • All three types of FHH are inherited in:
        • An autosomal dominant manner
      • In rare cases, FHH may be caused when a person’s immune system mistakenly makes antibodies that attack the CaSR protein:
        • The autoimmune form of FHH is not known to be caused by changes in a specific gene
      • Diagnosis of FHH:
        • Is suspected by high levels of calcium in the blood:
          • Especially when there are no other symptoms present
        • Further blood and urine tests may be used to rule out other possible causes
        • Genetic testing can confirm the diagnosis of FHH, except in rare autoimmune cases
      • Treatment:
        • Is typically considered unnecessary because most people with FHH do not have symptoms
        • If pancreatitis occurs, removal of the parathyroid gland may be recommended
    • Isolated familial PHPT
• Management of inherited PHPT:
  • In many cases PHPT is the first manifestation of a hereditary syndromic disease:
    • Goal of surgery is to normalize PTH and provide best chances for long term disease free outcome
  • Pitfalls in imaging in patients with MEN type 1:
    • Present with parathyroid gland asymmetry:
      • Most of this cases are secondary to hyperplasia not adenoma
  • The gold standard for the management of MEN type 1 is:
    • Bilateral neck exploration with a subtotal parathyroidectomy or total parathyoidectomy with autotransplantation (to the sternocleidomastoid muscle of the neck or the brachioradialis muscle of the forearm):
      • Biochemical cure are very similar between both approaches
      • With autotransplantation there is a 3% to 10% risk that the autotransplanted gland does not take leading to hypoparathyroidism:
        • For this reason cryopreservation might be a good option (they can be kept in this state for up to 2 years)
    • Remember that 3% to 5% of the cases of MEN type 1 might have super numerary glands:
      • This glands might hide in the thymus / thryothymic ligament or other ectopic locations
  • Intraoperative PTH measuring:
    • Allows us to decide how much of a gland remnant can be left behind to achieve longterm cure:
      • Achieving a intact PTH less that 40 pg/dl supports a longer long term free of recurrence
    • If the intraoperative PTH is very low it can helps us decide to autotransplant a gland to decrease that incidence of postoperative permanent hypoparathyroidism
  • Management of MEN type IIa:
    • All of this patients will have manifested with medullary thyroid cancer (MTC) or will be diagnosed with MTC and PHPT at the same time
    • The operative report of the thyroid cancer case is required along with the pathology report:
      • Talking with the surgeon that performed the thyroidectomy will be beneficial
    • At least two localizing studies that are concordant
    • Use cryopreservation in re due cases:
      • Because we might not have the information of how many glands were removed or injured during the thyroid surgery
    • Autotransplantation might be a good option when managing PHPT because MTC commonly recurs in the neck
    • If operating for the MTC and PHPT at the same time:
      • The surgery for PHPT remove the abnormal gland check intraoperative PTH (make sure it is normal) and leave the rest of the normal glands in situ
    • If subtotal thyroidectomy is performed:
      • Leave a portion of a gland that is about the same size as a normal gland
      • Make sure it is well vascularized
      • If possible leave an inferior gland:
        • They are easier to localize than a superior gland in re due cases
        • Prevents deep dissection close to the RLN in re due cases

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