Primary Hyperparathyroidism

  • 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

#Arrangoiz #ParathyroidSurgeon #ParathyroidExpert #Hyperparathyroidism #HereditaryHyperparathyroidism #HeadandNeckSurgeon #CancerSurgeon #SurgicalOncologist #PHPT #MENSyndromes

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s