| How is parathyroid embryology? | Inferior (-The inferior parathyroid glands = PIII, because they arise from the dorsal wing of the third pharyngeal pouch
-This common origin is why the PIII = thymic parathyroids and the two structures are described as the parathymus)
Superior (-The superior parathyroid glands are also known as PIV, because they arise from the fourth pharyngeal pouch
-The fourth pharyngeal pouch giving rise to the ultimobranchial body
-Due to this close origin with the lateral thyroid, the superior parathyroids are sometimes called the thyroid parathyroids However, it migrates far less than the PIII
-Because of the shorter migration length, PIV are in a more constant location than the PIII
-The PIV are generally located more posterior and medial than the PIII
-Histologically= chief cells and oxyphil cells) |
| What are clinical correlations w/parathyroid embryology? | -Accessory or supernumerary parathyroid glands are found in approximately 13% of individuals at autopsy
-These glands most likely result from tissue fragmentation that occurs during the migration
-The former typically weigh less than 50 mg, while true supernumerary glands have an average weight of 24 mg
-Absence of parathyroids (ie, < 4 glands) is noted in approximately 3% of individuals at autopsy Ectopic parathyroid glands occur in 15-20% of patients
-The glands may be located anywhere near or even within the thyroid or thymus
-For example, if parathyroid III do not descend entirely, they may be located as high as the bifurcation of the common carotid artery
-Conversely, if parathyroid III do not release from the thymus, they may be located intrathoracically, as low as the aortopulmonary window
-Other common ectopic locations include the anterior mediastinum, posterior mediastinum, and retroesophageal and prevertebral regions |
| How is appearance of parathyroid glands? | Shape (ovoid, polypoid, spherical)
Color (yellowish brown)
Size (6.3.2 mm)
Wt (35-50mg) |
| What are parathyroid diseases? | . |
| What are causes of hyperPTH? | . |
| Classification of causes of hyperPTH? | . |
| What is primary hyperPTH? | Definition of problem
-PH is the unregulated overproduction of parathyroid hormone (PTH) resulting in abnormal Ca homeostasis.
Frequency
-Prevalence of PH=21 cases per 100,000 person-years
-The mean age at diagnosis=between 52 and 56 years
-Female-to-male ratio of 3:1 |
| What are etiologies of hyperPTH? | -In 85% of cases=single adenoma
-In 15% of cases=multiple glands are involved(multiple
adenomas or hyperplasia)
-Rarely=parathyroid carcinoma
-The etiology of adenomas or hyperplasia=unknown
-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) |
| How is clinical presentation of hyperPTH? Hx | -The clinical syndrome can be easily remembered as "bones, stones, abdominal groans, and psychic moans“
-Routine measurement Ca = the most common clinical presentation changed from severe bone disease or kidney stones to asymptomatic hyperCa
= primarily a selective cortical bone loss
-Bone and joint pain, pseudogout, and chondrocalcinosis have also been reported
-In the early clinical descriptions, some patients developed osteitis fibrosa cystica, (increased generalized osteoclastic bone resorption)
-Radiographic plain film changes associated with osteitis fibrosa cystica include subperiosteal resorption in the phalanges and a finding known as salt and pepper skull
-This presentation is rarely seen today except in medically underserved populations |
| What are manifestations of primary hyperPTH? | ▪ Renal manifestations =polyuria, kidney stones,
hypercalciuria, and rarely nephrocalcinosis
▪ Skeletal manifestations
▪ Gastrointestinal manifestations = anorexia, N/V,
abdominal pain, constipation, peptic ulcer, and acute pancreatitis
▪ Neuromuscular and psychologic manifestations = proximal
myopathy, weakness and easy fatigability, depression,
▪ Cardiovascular manifestations = hypertension,
bradycardia, shortened QT interval, and left ventricular hypertrophy |
| How is workup labs
of primary hyperPTH? | -Total serum Ca, albumin levels or ionized Ca levels should be measured
-HyperCa should be documented on more than one occasion
-Intact PTH level = core of the diagnosis
-An elevated intact PTH level with an elevated ionized serum Ca level is diagnostic of primary hyperparathyroidism
-A 24-hour urine Ca measurement is necessary to rule out FHH
-Mild hyperchloremic acidosis, hypophosphatemia, and
mild to moderate increase in urinary Ca excretion rate
-Vitamin D levels should be measured in the evaluation of
PH
-Vitamin D deficiency can cause secondary
hyperparathyroidism and repletion of vitamin D deficiency
can help to reduce PTH |
| How is difference between hyperPTH etiologies on labs? | . |
| How are labs of differentials of PH? | . |
| What are imaging studies for hyperPTH? | -Imaging studies are not used to make the diagnosis of
PH(which is based on laboratory data)
-Imaging studies are not used to make a decision about
whether to pursue surgical therapy (which is based on
clinical criteria)
-Imaging studies are used to guide the surgeon once surgical therapy has been decided
-If a limited parathyroid exploration is to be attempted, a
localizing study is necessary
-Other uses of imaging studies in the initial evaluation of a
patient with primary hyperparathyroidism are controversial |
| What is use of US in hyperPTH? | -Ultrasonography = safe and widely used technique
-It is capable of a high degree of accuracy, but it is
operator dependent
-One advantage of neck ultrasonography is that it can
be performed rapidly by the clinician at the time of the
initial evaluation
-The accuracy =75-80%
-Ultrasound=not been reliable in detecting multigland
disease |
| What is use of MIBI? | -Nuclear medicine scanning with radiolabeled sestamibi
MIBI = accumulate in parathyroid adenomas
-This radionuclide is concentrated in thyroid and
parathyroid tissue but usually washes out of normal thyroid
tissue in under an hour
-It persists in abnormal parathyroid tissue
-On delayed images, an abnormal parathyroid is seen as a
persistent focus of activity
-The scan's sensitivity for solitary adenomas = 60-90%
-The main weakness of this test is in diagnosing
multiglandular disease (sensitivity 50%) |
| What is use of SPECT? CT and MRI? | -Most modern sestamibi scans are performed with singlephoton computed tomography (SPECT)
-This technique combines the detection of the radioactivity
with the detailed imaging of CT scanning, allowing better
sensitivity and more precise anatomic localization than
standard planar imaging
-CT scanning and magnetic resonance imaging (MRI) have
also been used also to locate abnormal parathyroid glands
-Standard CT scanning has inadequate sensitivity
-Newer techniques of CT scanning with dynamic contrast
images (4D-CT) have shown promise, with accuracy rates as high as 88%
-MRI can be useful, particularly in cases of recurrent or
persistent disease and in ectopic locations such as the
mediastinum |
| What are other imaging techniques used? | Arteriography
-PET CT Scan
-Bilateral internal jugular vein sampling is used to help
localize ectopic parathyroid adenomas; however, this
technique should generally be reserved for centers with
specialists and for selected patients |
| How is tx of primary hyperPTH? | -Surgical excision of the abnormal parathyroid glands = the only permanent, curative treatment for PH
-There is universal agreement that surgical treatment should be offered to all patients with symptomatic disease
-Some controversy exists regarding the optimal management of asymptomatic patients
Management of severe hyperCa in the acute setting
-Reduction of elevated serum Ca can be accomplished by the use of intravascular volume expansion with sodium chloride and loop diuretics such as furosemide once the intravascular volume is restored
-Drugs such as calcitonin and IV bisphosphonate have been
used as a temporary measure prior to surgical treatment |
| How is non-surgical care and long term monitoring for primary hyperPTH? | -Asymptomatic patients who do not undergo surgery require
long-term monitoring
-Recommendations include assessing for overt signs and
symptoms of PH annually, annual serum Ca and creatinine
testing, and bone mineral density (spine, hip, and
forearm) evaluation every 1-2 years |
| How is pharmacotherapy of hyperPTH? | -Estrogen therapy in postmenopausal women has been
shown to cause a small reduction in serum Ca (0.5-1
mg/dL) without a change in PTH
-Estrogen also has beneficial effects of lumbar spine and
femoral neck bone mineral density (BMD)
-Bisphosphonates, in particular alendronate, has been shown to improve the BMD at the spine and hip BMD in patients with PH
-Calcimimetic drugs activate the Ca-sensing receptor and
inhibit parathyroid cell function
-Treatment with cinacalcet resulted in reduction without
normalization of PTH levels, reduction and even
normalization of serum Ca, but no increase in BMD was
observed |
| What are other tx of PH? | -Percutaneous alcohol injection, ablation with ultrasound
energy, and other percutaneous ablation techniques =
alternative treatment in PH who cannot or will not
undergo surgery
-Percutaneous techniques = high complication rates,
mainly because of the close proximity to the recurrent
laryngeal nerve, particularly for the superior glands
-Routine use of these percutaneous techniques cannot yet
be supported |
| How is surgical care of PH? | -Surgical treatment should be offered to most patients with
PH
-The historical criterion-standard operative approach is
complete neck exploration with identification of all
parathyroid glands and removal of all abnormal glands
-Approximately 85% of cases of PH are caused by a single
adenoma
-Therefore, most patients who undergo full neck
exploration to evaluate all parathyroids endure some
unnecessary dissection
-Rather than explore all parathyroid glands, a newer
technique, directed parathyroidectomy, has evolved
-This technique relies on preop imaging studies to localize
the abnormal gland
The surgeon then removes only that gland, without
visualizing the other glands |
| How is surgical care part 2? | With sestamibi scanning or US, an abnormal parathyroid
detected =70-80% of cases
-Intraop PTH assay
-Because the plasma half-life of PTH=approximately 4
mins, the level falls quickly after resection of the source
-If the level fails to fall after resection of the identified
abnormal gland, the procedure is extended to allow for
further exploration
-A few authors have advocated radio-guided
parathyroidectomy, detecting the labeled sestamibi in the
abnormal gland using a handheld probe |
| How is surgical care of PH part 3? | -Parathyroidectomy is usually well tolerated
-The main risks are injury to the recurrent laryngeal nerves and hypoparathyroidism
-Although local anesthesia has been used successfully for this procedure, especially in the directed approaches during which a single adenoma is localized preop, GA is used most commonly
-Abnormally enlarged glands are excised after confirmation of the normal size of other glands
-During excision, avoiding capsular rupture of the abnormal gland is important because this may be associated with implantation of parathyroid cells in the operative site and subsequent parathyromatosis |
| How is surgical care of PH part 4? | -Parathyroids may be identified by highly experienced surgeons based on appearance and location
-In most cases, identification of the parathyroid glands should be confirmed histologically by frozen section examination
-In cases of subtotal or total parathyroidectomy with autotransplantation, parathyroid tissue should be cryopreserved for future autotransplantation in case the initial transplant does not function adequately |
| What are complications and postop care of PH? | -For a full parathyroid exploration, postop hypoparathyroidism and hypoCa are concerns
-The nadir of serum Ca usually occurs 24-72 hours postop
-Many patients become hypoCa, but few become symptomatic
-HypoCa after parathyroid surgery may be due to hungry bone syndrome where Ca and P are rapidly deposited in the bone
-This is characterized by hypoparathyroidism and transient, but occasionally severe, hypoCa until the normal glands regain sensitivity |
| What are other complications and postop care of PH? | -If hypoparathyroidism persists, oral supplementation with
calcium and vit D is required
-Ca citrate or Ca carbonate may be started at 2 tbs 4 times per day
-Some patients require substantially more
-Calcitriol is started at 0.5 mcg twice daily and increased as required
-Patients in whom total parathyroidectomy and
autotransplantation is performed can be expected to require A potential life-threatening emergency in the postop period is the development of an expanding hematoma in the pretracheal space
-This complication=treated immediately by opening the wound and evacuating the hematoma
-If untreated, laryngeal edema may progress rapidly, causing airway obstruction
-Most small hematomas do not require treatment
-A subplatysmal fluid collection may occasionally form, and these are usually treated adequately with a single aspiration
-In a few cases, aspiration may need to be repeated |
| How is followup of hyperPTH? | Patients are seen 1-2 weeks postop, and serum Ca, 25-
hydroxyVit D levels, and PTH levels are obtained
-PTH levels may be elevated postop in some patients, but if the serum Ca remains within the reference range, it does not indicate persistent disease in most patients
-Many of these patients have vitamin D deficiency, and
replacement may correct the elevated PTH concentration |
