​Kembara Xtra - Medicine - Hyperparathyroidism

​Kembara Xtra - Medicine - Hyperparathyroidism 
an abnormality in the body's regular regulatory feedback processes that causes an overproduction of parathyroid hormone (PTH)

Primary hyperparathyroidism (HPT) is characterized by excessive PTH release as a result of intrinsic parathyroid gland malfunction and a failure to respond to calcium-induced feedback inhibition.
The proper increase in PTH production in response to possible hypocalcemia and/or hyperphosphatemia is known as secondary HPT. Lack of vitamin D, kidney disease, low calcium intake, poor calcium absorption, and/or phosphate loading can all contribute to this. Tertiary HPT: autonomous hyperfunction of the parathyroid gland in the setting of long-term secondary HPT

Female > male (3:1) Predominantly postmenopausal females Epidemiology Incidence
Prevalence
In the US, primary HPT affects 1 in 500 to 1 in 1000 people.

Pathophysiology and Etiology 

PTH is primarily controlled by calcium concentrations.
The four parathyroid glands, which can be found behind the thyroid's four poles in different places, produce PTH.
Ectopic or supernumerary glands (more than four glands), which are most frequently found in aberrant sites.
PTH stimulates osteoclastic activity, which increases bone resorption, and releases calcium from bone.
PTH boosts the reabsorption of calcium in the kidneys' distal tubules.
PTH enhances the conversion of 25-hydroxycholecalciferol (25[OH]D) to 1,25-dihydroxycholecalciferol (1,25[OH]2D or active vitamin D) in the kidneys, increasing phosphorus excretion by reducing reabsorption. 1,25(OH)2D enhances osteoclastic activity and bone resorption in addition to increasing calcium and phosphate absorption from the GI tract and kidneys.
Primary HPT: Uncontrolled PTH generation and release as a result of the absence of the extracellular calcium's usual feedback regulation, which results in an increase in serum calcium.
- One-sided adenoma (80–85%)
- Multiple endocrine neoplasia (MEN) type I or MEN type IIA, which may occur sporadically or in conjunction with diffuse hyperplasia (10–15%) of the four parathyroid glands.
- Dietary changes - Secondary HPT: adaptive parathyroid gland hyperplasia and hyperfunction due to reduced calcium - Parathyroid carcinoma (1%), a very rare and severe form -
A lack of vitamin D reduces the body's ability to absorb calcium.
Chronic renal illness brought on by a calcium shortage causes the following symptoms:
Loss of the renal parenchyma results in hyperphosphatemia.
 Hypocalcemia resulting from impaired calcitriol synthesis
General resistance to PTH in the skeletal and renal systems Tertiary HPT: autonomous oversecretion of PTH after protracted parathyroid stimulation

Genetics MEN type I and MEN type IIA: MEN-I gene mutation screening should be performed on patients with multiple gland hyperplasia who do not also have renal illness.
Infants born missing both calcium-sensing receptor (CaSR) gene alleles have neonatal severe primary HPT.
Familial hypocalcciuric hypercalcemia (FHH): deletion of one CaSR gene allele. HPT—jaw tumor syndrome.
Isolated familial HPT


Risk Elements 
Age-related renal disease, inadequate nutrition, radiation exposure, and/or family history

Prevention 
Calcium and vitamin D consumption should be adequate to prevent subsequent HPT.

Associated Conditions include chronic renal failure, vitamin D insufficiency, and the MEN I and MEN IIA syndromes.


Asymptomatic patients make up about 80% of people with histories of current illness.
stones in the kidney (15–20%)
- Osteitis fibrosa cystica (5%), characterized by "salt and pepper" appearance of the head, tapering of the distal clavicles, bone cysts, and brown tumors of long bones.
- Hypercalcemia symptoms such as mental confusion, memory loss, polyuria, polydipsia, constipation, bone pain, poor focus, altered mental status, weariness, and muscle weakness
Past medical history - The following illnesses may be linked to HPT: MEN syndrome (MEN I linked to pituitary adenomas, pancreatic cancers, and parathyroid hyperplasia; MEN IIA linked to medullary thyroid cancer, pheochromocytoma, and parathyroid hyperplasia); nephrolithiasis (in 20-30% of cases); nephrocalcinosis; pancreatitis; gastro


clinical assessment 
Physical findings that are connected to the underlying cause of HPT may be discovered. Limited usefulness; 70–80% of patients have no visible symptoms or indicators of disease.

Differential Diagnosis: PTH Production Increased: Ectopic PTH production is uncommon. It confirms the diagnosis of primary HPT in the majority of instances, but first, rule out:
– FHH: A 24-hour urine calcium:creatinine ratio can rule out FHH.
Lithium and thiazide diuretics

Causes of nonparathyroidism
Multiple myeloma, lymphoma, leukemia, prostate cancer, Paget disease, and lung (squamous cell) carcinoma are examples of malignancies. Granulomatous illnesses include sarcoidosis, TB, berylliosis, histoplasmosis, and coccidioidomycosis.
- Drugs: milk-alkali syndrome and vitamin D poisoning
- Endocrine: acute adrenal insufficiency and hyperthyroidism

Laboratory Results 

Initial examinations (lab, imaging)
Frequently discovered by unintentional hypercalcemia on standard lab tests. Checking ionized calcium is the best method.

 To calculate adjusted calcium, multiply the patient's albumin level by 0.8 and the serum calcium value in mg/dL. Since the uncorrected calcium is normal, some people may have mild hypercalcemia for years without it being noticed.
If hypercalcemia is verified, check your PTH level next.
- PTH dependent: Primary HPT is suggested by high or (abnormally) normal PTH.
PTH-independent hypercalcemia is indicated by undetectable or low PTH levels.
● Low serum phosphate and significant 24-hour urine calcium excretion are possible additional results.
● A high phosphorus level in secondary HPT indicates chronic renal failure; a low phosphorus level indicates another cause, typically a 25(OH)D shortage. Both of these are frequent reasons for increased PTH levels in the presence of normal adjusted calcium levels.

Tests in the Future & Special Considerations
A ratio of >0.02 between the 24-hour urine calcium concentration and creatinine clearance and 0.01 between the two may indicate FHH, which is a significant result because FHH does not require surgery.

All individuals with primary HPT should have their 25(OH)D levels routinely checked. Delay making management decisions in cases of vitamin D deficiency (20 ng/mL or 50 nmol/L) until levels are kept >20 ng/mL (50 nmol/L).

Other/Diagnostic Procedures
Diagnostic imaging is not necessary. Planning for surgery is necessary, particularly for minimally invasive parathyroidectomies (MIP).
- Imaging is also recommended for repeat surgery to pinpoint hyperplasia or an ectopic parathyroid gland.
Imaging techniques for localization prior to surgery
- Technetium-99m sestamibi with or without single-photon emission computed tomography (SPECT): It is frequently wrong in multigland illness but has the highest reported success rate for localizing solitary parathyroid adenomas.
- Neck ultrasound (US): painless, noninvasive, and radiation-free; however, operator skill is required for accuracy.
- Four-dimensional CT (4D-CT) may be superior to sestamibi-SPECT and US for primary localisation.
- In terms of diagnostic usage, positron emission tomography (PET) with C-methionine (MET-PET) is comparable to US and technetium-99m sestamibi with SPECT.
- The most common methods for locating ectopic mediastinal glands are CT and MRI.

Medication Primary HPT: Operative management is curative; the following are the indications for surgical surgery.
For individuals who cannot or are awaiting surgery:
- Bisphosphonates (alendronate): Help to preserve bone density and decrease bone turnover; avoid in kidney disease (GFR 35).
CaSR in the parathyroid gland is activated by calcimimetics (cinacalcet) (1)[B], which inhibits PTH secretion. No long-term data on its impact on constitutional, cognitive symptoms, or fractures; FDA-approved for symptomatic individuals who are not surgical candidates.
- Raloxifene, a selective estrogen receptor modulator, inhibits PTH-mediated bone resorption
– The benefits of estrogen replacement therapy must be weighed against the dangers of recognized systemic side effects; it is not advised as a first-line treatment.
○ Can be utilized by postmenopausal women who reject or do not undergo surgery
Secondary HPT: The underlying cause is frequently the focus of treatment.
- Calcium replenishment - Analogs of vitamin D (calcitriol and paricalcitol)
- Sevelamer, a phosphorus-binding agent
Calcimimetic (cinacalcet) - Tertiary HPT - Medical treatment is generally not recommended and is not curative.

Surgical Procedures 95–98% of patients with primary HPT respond to operational management. It is the initial line of pediatric treatment. Additionally, it is frequently the initial course of treatment for young adults up to 50 years old.

Parathyroidectomy indications include primary HPT symptoms, nephrolithiasis, and fragility fractures.
Osteitis fibrosa cystica - primary HPT without symptoms
Age 50 years Serum Ca+ level >1 mg/dL above normal
24-hour urine calcium >400 mg/day (>10 mmol/day) and increased stone risk by biochemical stone risk analysis are associated with creatinine clearance 60 mL/min.
Nephrolithiasis or nephrocalcinosis found on an x-ray, an ultrasound, or a CT scan
 Bone density reduction in the lumbar spine, femoral neck, whole hip, or distal third of the radius with a T-score of less than 2.5
The only confirmed curative treatment for HPT is surgical excision of the affected gland or tissue.
The following surgical options are available:
- MIP using intraoperative PTH levels (high sensitivity 79-95% to predict location of single parathyroid adenoma) and preoperative sestamibi scan with SPECT/US/4D-CT, which results in less pain, smaller incisions, improved cosmetic results, lower morbidity, and a shorter hospital stay than open neck exploratory surgery.
Follow postoperative serum calcium, magnesium, and phosphorus levels; keep an eye out for the "hungry bone" syndrome associated with hypocalcemia.
Patients may require oral calcitriol and calcium supplements first, followed by an IV calcium infusion postoperatively.
Though it is currently less prevalent, hungry pain syndrome can be extremely severe.
Additionally, hemorrhage and airway compromise concern for patients
Keep a close eye on renal function.

Admission 
For severe symptoms caused by critical hypercalcemia, IV fluid rehydration, IV bisphosphonate treatment, and SC calcitonin (4 U/kg q12h) are all necessary.

Take Action 
Calcium and PTH levels need to be serially monitored in asymptomatic patients with primary HPT.
patient observation
A bone density scan every one to two years and annual measurements of blood calcium and creatinine are enough for patients with primary HPT who are asymptomatic.


Diet
Dietary calcium limitation is advised in cases of hypercalciuria or increased 1,25(OH)2D levels.
Otherwise, a maximum of 1,000 mg of calcium should be consumed per day.
Limit the phosphate in your diet for secondary HPT.


The significance of routine lab examinations Symptoms of severe hypercalcemia

Prognosis In primary HPT, the prognosis is excellent following surgery thanks to the elimination of several preoperative symptoms.

Complications Associated with Elevated Calcium and/or High PTH Levels