​Kembara Xtra - Medicine - Hypoparathyroidism

​Kembara Xtra - Medicine - Hypoparathyroidism 
Acute hypoparathyroidism causes tetany that can be mild (muscle cramps, perioral numbness, paresthesias of the hands and feet), severe (carpopedal spasm, laryngospasm, heart failure, seizures, stridor), or absent (deficient or absent parathyroid hormone, or PTH) secretion.
Chronic: frequently asymptomatic; lethargy, anxiety, and depression; renal impairment and urolithiasis; dementia; fuzzy vision from cataracts or keratoconjunctivitis; parkinsonism or other movement disorders; mental retardation; dental abnormalities; and dry, puffy, coarse skin
Endocrine/metabolic, musculoskeletal, neurological, ophthalmologic, and renal are the system(s) affected


Pediatric Concerns May affect premature newborns Neonates born to hypercalcemic mothers may undergo inhibition of the parathyroid glands throughout development.
Congenital parathyroid absence may manifest later in infancy as an autoimmune condition.

Aspects of Geriatrics

Although it happens infrequently, hypocalcemia rarely results from hypoparathyroidism in the elderly.

pregnant women's issues
The tocolytic use of magnesium may result in functional hypoparathyroidism.
During lactation, calcitriol requirements for hypoparathyroid women decrease.

Epidemiology 
All ages are affected; more prevalent in women
Incidence
Most prevalent after anterior neck surgery, especially when the surgeon only conducts a small number of anterior neck dissections (50–100 thyroid/parathyroidectomies each year).
Permanent hypoparathyroidism varies depending on the surgeon and the facility's experience, although transient hyperparathyroidism is frequent (6.9-46% of thyroidectomies).

Prevalence Genetic diseases account for 10% of all hypoparathyroidism, but represent a significant number of cases in children. Affects 24 to 37/100,000 people annually in the United States.

Pathophysiology and Etiology
PTH helps control calcium homeostasis:
- Releases calcium and phosphorus from bone reserves - Promotes the production of 1,25-dihydroxyvitamin D, which increases calcium absorption from the gut
- Stimulates phosphate excretion in the proximal tubule and calcium reabsorption in the distal convoluted tubule. - Reduced or absent PTH activity causes hypophosphatemia, hypercalcemia, and hypercalciuria.
acquired hypoparathyroidism - surgical removal or harm to the parathyroid glands' blood supply or enervation during neck surgery for thyroid or parathyroid removal or neck surgery for head and neck malignancy (2)
- Autoimmune: Polyglandular autoimmune (PGA) condition, alone or in combination with other endocrine deficits
- Deposition of heavy metals in the gland, including iron (hemochromatosis, thalassemias), copper (Wilson disease), and metastatic infiltration; radiation-induced damage; and
Because magnesium is essential for PTH secretion and PTH receptor activation, functional hypoparathyroidism may be caused by hypo- or hypermagnesemia.
- Congenital TBCE gene mutations, aberrant PTH secretions, HDR or Barakat syndrome, anomalies of the calcium-sensing receptor (CaSR), hypocalcemia with hypercalciuria, familial mutations of the TBCE gene, and 22q11.2 deletion syndrome
Genetic gain-of-function mutation in CaSR associated with autoimmunity
Metastatic cancer, hemochromatosis, Wilson disease, and granulomas are infiltrative conditions.

Genetics Mutations in the transcription factor glial cell missing B (GCMB), which are X-linked or autosomal recessive
Mutations in transcription factors or regulators of parathyroid gland development - Part of a more severe genetic syndrome (APS-1 or DiGeorge syndrome) or occurring alone (X-linked hypoparathyroidism) - May be autosomal dominant (DiGeorge), autosomal recessive (APS-1), or X-linked recessive (X-linked hypoparathyroidism)
- Genetic disorders
hereditary hypomagnesemia, hypoparathyroidism with lymphedema, and 22q11.2 deletion syndrome
Hypoparathyroidism with sensorineural deafness PGA syndrome type I: mucocutaneous candidiasis, hypoparathyroidism, and Addison disease ADHH: mutations gain-of-function of the CaSR gene inhibiting the parathyroid gland, without increase of PTH

Risk factors include neck cancer, neck surgery, neck injuries, PGA syndrome, and family history of hypocalcemia.

Prevention 
Identification and preservation of parathyroid tissue during surgery

Associated Conditions: Addison disease, juvenile familial endocrinopathy, DiGeorge syndrome, Bartter syndrome, PGA syndrome type I, multiple endocrine deficiency autoimmune candidiasis (MEDAC) syndrome, and moniliasis (HAM) syndrome, a polyglandular deficiency syndrome that may be genetic and is characterized by hypoparathyroidism.

Introducing History 

Ask about previous neck injuries or surgeries, head or neck radiation, family history of hypocalcemia, or the existence of other autoimmune endocrinopathies as these are frequently asymptomatic.
Fatigue, circumoral or distal extremities paresthesias, muscle spasm, convulsions, and neuropsychiatric symptoms are all included in the list of clinical symptoms.

clinical assessment 
Neck scar from surgery
When the facial nerve on the cheek is touched, the upper lip will twitch ipsilaterally as the Chvostek sign. 15% of persons with normocalcemia have a positive indication.

Trousseau sign: painful carpal spasm following 3-minute brachial artery closure with blood pressure cuff. Carpal spasm (flexion of the metacarpophalangeal (MCP) joints, extension of the interphalangeal (IP) joints, and adduction of the fingers and thumb) is caused by inflating the blood pressure cuff over the systolic level for three minutes.
Tetany, broncho- or laryngospasm, arrhythmias of the heart, refractory heart failure, dyspnea, and edema
Dry, flaky, puffed-up hair and brittle nails
Deep tendon reflex loss, dysrhythmias (secondary hypocalcemia), cataracts or ectopic calcifications, tooth enamel abnormalities, vitiligo, and other conditions are just a few examples.

Deficiency or resistance to vitamin D is the differential diagnosis
Pseudohypoparathyroidism, which manifests in childhood and is characterized by kidney and bone insensitivity to PTH; hypocalcemia; hyperphosphatemia; and, unlike hypoparathyroidism, raised rather than decreased PTH concentrations.

Malabsorption, hypoalbuminemia, familial hypocalcemia, renal failure, and hypomagnesemia

Initial test results from the laboratory and imaging

Low ionized and total calcium (Accurate serum calcium level for albumin).
- Total serum calcium plus 0.8 (4 times serum albumin) equals corrected serum calcium.
High phosphorus
Distinguish from pseudohypoparathyroidism or other secondary causes; intact or "whole" PTH: low
Magnesium levels: low or average
BUN and creatinine levels should be monitored, particularly in older patients.
25-OH vitamin D level: Hypoparathyroidism might get worse if vitamin D levels are low.

 Normal or excessive urinary calcium levels

After thyroid or parathyroid surgery, calcium levels should be monitored, especially during the operation. Radiographs may reveal missing tooth roots, calcification of the cerebellum, choroid plexus, or cerebral basal ganglia.

Tests in the Future & Special Considerations
ECG: prolonged ST and QTc intervals, repolarization alterations that are not specific, dysrhythmias
Urine calcium: Creatinine ratio (about 0.1 to 0.2) should be monitored to prevent stones brought on by hypercalciuria.
Gene sequencing: To diagnose APS-1, it may be necessary to assess the levels of additional hormones.
(Transient hypoparathyroidism following parathyroid surgery) Hungry bone syndrome Despite a rebound in PTH secretion from the remaining normal glands, hungry bone syndrome-related hypocalcemia may still exist. Therefore, serum PTH levels could be low, normal, or even high.
Prostate, breast, or lung cancer osteoblastic metastases; consider using the right imaging.
Of 73 patients with APS-1 and hypoparathyroidism, autoantibodies against NACHT leucine-rich-repeat protein 5 (NALPS) were discovered in 49% of cases.

Management 

ECG monitoring while calcium replacement.
Maintenance therapy: may call for a lifetime of calcium and calcitriol administration - Keep the serum calcium level within the low normal range, which is 8 to 8.5 mg/dL (2 to 2.12 mmol/L).
If hypercalcemia develops, medication should be postponed until calcium levels are normal. If magnesium insufficiency is present, treat it.
If the product has a significant calcium-phosphate content, phosphate binders are necessary.
Oral calcium supplements and vitamin D supplementation after thyroidectomy may lessen the risk for symptomatic hypocalcemia following surgery. Thiazide diuretics combined with a low-salt diet may be used to prevent hypercalciuria, nephrocalcinosis, and nephrolithiasis.

Treatment for acute hypoparathyroidism: Tetany, convulsions, heart failure, laryngospasm, and bronchospasm are among the severe symptoms of this condition.
1 or 2 g of calcium gluconate IV infusions over a 10-minute interval. Because calcium-containing fluids might irritate adjacent tissues, central venous catheters are suggested. Then, at a rate of 1 to 3 mg calcium gluconate per kg of body weight per hour (2)[B], infuse 10 g of calcium gluconate into 1 L of 5% dextrose water.
Chronic hypoparathyroidism - Hypomagnesemia: initially, 1 to 2 g IV every six hours; long-term, once or twice daily 600 mg magnesium oxide tablets

Initial Line
Adults: Calcium carbonate taken orally is favored due to its high elemental calcium concentration; for improved absorption, discontinue using PPIs and take it with meals.
For people taking PPIs and those taking calcium carbonate for constipation, oral calcium citrate is preferable.
The recommended starting dose of elemental calcium is 1 to 3 g per day, although quantities might vary greatly.
Calcitriol, or 25-dihydroxycholecalciferol, is the preferred form of vitamin D replacement; doses of 0.25 to 2.0 g/day are typically needed.

Take into account using a thiazide diuretic for hypercalciuria.
Use a low phosphate diet or phosphate binder if your phosphate level is significantly higher than usual (>6.5 mg/dL).
Children should take 25 to 50 mg/kg of elemental calcium or 0.25 g of calcitriol daily if they are older than one year old.


Endocrinologist referrals include those to nephrologists for kidney disease or recurring stones, ophthalmologists for eye problems, and geneticists for inherited issues.

Further Treatments 
PTH peptides 1-34 and 1-84 SC; rhPTH 1-84—FDA-approved, 50 g SC daily; For patients with frequent episodes of hyper- and hypocalcemia; nephrolithiasis; nephrocalcinosis; GFR 60 mL/min; persistently high phosphate; Treatment goal: Eliminate use of active vitamin D3; reduce supplemental calcium to 500 mg daily; maintain consistent calcium level in low normal range.


Surgical Techniques 
Cryopreserved parathyroid tissue autotransplantation recovers normocalcemia in 23% of instances.


Laryngospasm, seizures, tetany, and QT prolongation are admission requirements/initial stabilizing conditions. Resolution of hypocalcemic symptoms and patient education regarding hypoparathyroidism and treatment are discharge requirements.

Patient Follow-Up Monitoring
The target range for 24-hour urine calcium is 300 mg, total corrected serum calcium is 8.0–8.5 mg/dL or 2.00–2.12 mmol/L, and calcium-phosphate product is 55. Treat even if asymptomatic if calcium levels are below 2.0 mmol/L or 8.0 mg/dL.

 Weekly or every other week checks for medication adjustments; once stable, every six months; outpatient testing of blood calcium, phosphate, magnesium, and creatinine during initial management.

24-hour urine testing yearly for calcium and Cr secretion
Every five years, undergo a renal imaging exam if you have signs of renal stone disease or rising Cr.

It is advised to have annual slit-lamp and ophthalmologic exams.
DEXA scan: routine monitoring is advised (4)[B]
Low-phosphate diets are recommended for those with hyperphosphatemia.

Complications 
Reversible: caused by low calcium levels, most likely to get well with proper care
- Paresthesias (circumoral, fingers, toes), tetany, seizures, parkinsonian symptoms, and pseudotumor cerebri have all been reported as neuromuscular symptoms.
- Renal: nephrocalcinosis, nephrolithiasis, and hypercalciuria
- Cardiovascular: arrhythmias, heart failure
When a problem develops early in childhood and does not get better after taking calcium and vitamin D supplements, it is irreversible.
Growth retardation, tooth enamel abnormalities, and hypoplasia, atrophy, brittleness, and ridging of the nails, cataracts, and calcifications of the basal ganglia