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 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)* Ca++ mmol/L (40 – Alb)* 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 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 4 th 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.