parathyroid

The parathyroid glands

Dr. AMMAR SALIH ABBOOD
2016

The parathyroid glands

Parathyroid hormone (PTH) plays a key role in the regulation of calcium and phosphate homeostasis and vitamin D metabolism

Anatomy and physiology

Four glands lie behind the lobes of the thyroid.
The chief cells secret PTH which is a single chain polypeptide of 84 amino acids
Low ionised serum calcium will stimulate the chief cells via a “calcium sensing receptor” to secret PTH

Functions of PTH

Increase calcium reabsorption from renal tubules and decrease phosphate reabsorption
Increase osteoclastic bone resorption and bone formation
Stimulates alpha hydroxylase enzyme in the kidney and promotes the conversion of 25 HCC to 1,25 DHCC

Calcium and phosphorus

Calcium
Total body calcium is about 1200-2000 g.
* 99% in bones and teeth.
*1% circulates in the blood.
50% of circulating Ca is bounded to albumin.
The free Ca”ionised” is the biologically active form.
Blood level of Ca is 2.2–2.6 mmol/L (8.5–10.5 mg/dL).

Functions of Calcium

Bone mineralization.
Regulates hormonal and neuromuscular signaling.
Important in cardiac contractility.
Important for blood coagulation.


Hypocalcemia
Causes of Hypocalcemia:
Hypoparathyroidism
Pseudohypoparathyroidism
Vitamin D deficiency.
Chronic renal failure.
Drugs ( loop diuretics, bisphosphonates).
Acute pancreatitis.
Acute rhabdomyolysis.

Clinical feature of hypocalcemia

Mild : asymptomatic.
Moderate : paresthesias mainly affect fingers and perioral area (Chvostek's and Trousseau's signs may be seen).
Severe : seizures, carpopedal spasm, bronchospasm and laryngospasm may occur.
Clinical features of the underlying cause

Hypercalcemia

Causes of hypercalcemia:
Primary and tertiary Hyperparathyroidism.
Malignancies.
Granulomatous diseases (sarcoidosis, tuberculosis).
Endocrine disorders ( hyperthyroidism, Addison )
Drugs (thiazides).
Excessive calcium intake (Milk-alkali syndrome).
Familial hypocalciuric hypercalcemia


Clinical features of hypercalcemia
Mild : asymptomatic
Moderate :
*nausea, anorexia, constipation, polyuria.
*Renal stones.
*Peptic ulcer disease.
* neuropsychiatric symptoms.
Sever : lethargy, confusion and coma.

Investigations

Serum calcium.
Hypoalbuminaemia will falsely lower serum calcium level , so level needs to be corrected by adding 0.1 mmol/l (0.4 mg/dL) for each 5 g /L reduction in serum albumin below 40 g/L

(40 – Alb)* 0.02 + Ca++ mmol/L
(40 – Alb)* 0.08 + Ca++ mg/dL

Other investigations

ECG : QT interval.
Serum phosphate
Alkaline phosphatase
Renal function tests
PTH
25 HCC


Treatment
Correction of the underlying cause.
IV calcium gluconate for acute symptomatic hypocalcemia.
Oral calcium for chronic hypocalcemia with vitamin D.
Rehydration with or without diuretics for hypercalcemia
Bisphosphonates for hypercalcemia

Phosphorus

Total body phosphorus is about 600 g of which 85% present in bones.
It is also a component of structural proteins, enzymes, transcription factors, energy stores (ATP) and nucleic acids.
Blood level is 0.75–1.45 mmol/L (2.5–4.5 mg/dL).

Food sources of phosphorus

Hypophosphatemia

Causes of hypophosphatemia :
Primary hyperparathyroidism.
Vitamin D deficiency.
Renal loss of phosphate.
Drugs like aluminum containing antacids.


Clinical features of hypophosphatemia
With hypocalcemia : Bone pain, proximal muscle weakness and pseudofractures.
With hypercalcemia : renal stones , calcifications
Lethargy, confusion, disorientation, ataxia, Respiratory failure, cardiac dysfunction and Rhabdomyolysis may occur in sever cases.

hyperphosphatemia

Causes of hyperphosphatemia:
Renal insufficiency.
Hypoparathyroidism.
Extensive cellular injury or necrosis ( crush injury, rhabdomyolysis)

Clinical features of hyperphosphatemia

Widespread calcium phosphate precipitation leading to:
*Renal stones.
*Seizures.
*Pulmonary and cardiac calcifications.
Symptoms of hypocalcemia.

Diagnosis and treatment

serum phosphorus, serum calcium
Correct the underlying cause.
Hypophosphatemia : Oral phosphate for mild cases and IV phosphate for severe cases.
Hyperphosphatemia : Rehydration, Phosphate binders (sevalamer), Hemodialysis.


Hyperparathyroidism

Classification and Causes

Primary Hyperparathyroidism

Epidemiology
Prevalence 1 in 800
2-3 times more common in women
90 % of patients are over 50 years old
May be part of familial MEN syndrome

Clinical features

50% asymptomatic
Clinical features of hypercalcemia , polyuria, polydipsia, recurrent renal pain, constipation, dyspepsia, peptic ulceration, nausea, anorexia, lethargy, depression and impaired cognition
“ bones, stones and abdominal groans”

Clinical features

Osteitis fibrosa : bone resorption and fibrous replacement in the lacunae
Chondrocalcinosis: ca deposition in articular cartilage and secondary OA and Pseudogout
Nephrocalcinosis
Soft tissue calcification, vessels walls, hands and cornea


Investigations
Hypercalcemia
Hypercalciuria
Hypophosphatemia,
Raised PTH (fasting)
Normal renal function tests

Investigations

Skeletal X-rays:
Normal in early disease
Demineralization
Subperiosteal erosions and terminal resorption of phalanges
Salt and paper appearance on lat. skull x-ray
Osteopenia and osteoporosis by DEXA

Localization of the adenoma

Ultrasound
Neck MRI
99m Tc-sestamibi scintigraphy

Treatment

Surgery is indicated in :
Age <50
Ca >11.4 mg (2.85 mmol)
Presence of complications PU, stones etc.

Complications of surgery

“hungry bone syndrome “ is a profound hypocalcemia which develops after parathyroidectomy due to rapid remineralisation of bone before recovery of residual parathyroid tissue
This is prevented by calcium and active vitamin D supplements in the immediate post-operative period for 2-3 weeks

Treatment

Asymptomatic patients need follow up 6-12 monthly

Cinacalcet is a calcimimetic that enhance the sensitivity of Ca sensing receptors used for patients unfit for GA and for tertiary hyperparathyroidism

Familial hypocalciuric hypercalcemia

AD , defective Ca-sensing receptors
Presents with hypercalcemia, increased PTH and hypocalciuria
The hypercalcemia is always asymptomatic and no complications
Diagnosis by urine Ca and genetic testing
No treatment is required


Hypoparathyroidism

Causes

Damage to the glands or their blood supply during thyroid surgery 10% transient, 1% permanent
Polyendocine syndrome
Di George syndrome
Autosomal dominant hypoparathyrodism ADH (Hypocalcaemic hypercalciuria)
Abnormal infiltrations of the gland , Wilson's , hemochromatosis

Pseudohypoparathyroidism

Tissue resistance to PTH , patients are hypoparathyroid with elevated PTH , their features are short stature with short 4th metacarpals , round faces , obesity and subcutaneous calcifications ‘’ Albright’s hereditary osteodystrophy AHO “

Pseudo-pseudohypoparathyrodism

Same as AHO with normal Ca and PTH concentration
This disorder is an example of genetic imprinting, inheritance of defective gene from the mother leads to pseudohypopara, inheritance of the defective gene from the father leads to pseudo-pseudohypopara






Clinical features of hypoparathyrodism
Symptoms of Hypocalcemia
Decrease Calcium level
Increase phosphate level
PTH

Treatment

Oral calcium salts and vitamin D analogues either alfacalcidol or Calcitriol
Recombinant PTH is available.