PARATHYROID DISORDERS

Parathyroid glands develop from the 3^rd and 4^th branchial pouches and secrete Parathormone (PTH)-a polypeptide hormone with vital role in calcium metabolism along with Vitamin D and calcitonin (Fig.

PTH increases serum calcium levels by increasing its: (a) absorption from gut, (b) reabsorption from kidney, and (c) mobilization from bones. Renal action is mainly mediated by enhanced activity of 1-#945; hydroxylase enzyme, which facilitates synthesis of 1,25-dihydroxy- cholecalciferol-activated vit D.

PTHrP, a PTH homologue is produced in almost every cell of the body including embryonic tissues and activates PTH receptors. However, its role is more critical for maternal-fetal calcium transfer and normal fetal development.

Hypoparathyroidism, i.e. decreased PTH levels, is characterized by decreased serum calcium and elevated serum Phosphate levels, with/without clinical manifestations.

Etiology of hypoparathyroidism includes:

• Congenital parathyroid aplasia, as an isolated defect or with other malformations, e.g. DiGeorge syndrome.

• Autoimmune parathyroiditis, isolated or as a part of polyendocrinopathy type I.

• Iatrogenic injury during thyroid surgery/ irradiation or hemosiderosis (multiple transfusions in thalassemia)

• End-organ resistance (pseudohypoparathyroidism), as discussed later.

Transient hypoparathyroidism is common in new­borns of mothers with hyperparathyroidism and may present with neonatal tetany.

Clinical presentation may vary from: (a) asymptomatic hypocalcemia, to (b) early signs—muscle pain/cramps and paresthesia, (c) latent or manifest tetany, (d) recurrent seizures, or (e) chronic disease with dental abnormalities, cataract, growth/developmental retardation and mucocutaneous candidiasis.

Diagnosis depends on:

• Hypocalcemia with hyperphosphatemia, with normal, low or even high alkaline phosphatase levels,

• Decreased PTH levels on immunometric assay,

Radiological abnormalities, e.g. metaphyseal hyper­density in long bones and basal ganglia calcification on CT scan are present in ~ 50% cases.

Management of these cases include:

a. Emergency treatment of seizures/hypocalcemia with IV calcium 10% (1-2 ml/kg 6-hourly) along with IV/ PO Calcitriol 0.25 #956;g stat followed by 0.01-0.1 #956;g#8725;kg 12-hourly for 3-4 days, till serum calcium returns to normal. (Calcitriol is active Vitamin D, i.e. 1,25 (OH)2 D3)

b. Long-term control with PO Calcitriol 20 to 60 ng/kg/day and calcium 30 to 75 mg/kg/day, along with reduced intake of high phosphorus diet, i.e. milk, egg, etc.

DiGeorge syndrome is an important cause of congenital hypoparathyroidism with abnormal development of III and IV pharyngeal pouches due to microdeletion in chromosome 22 (22q11.2) and often associated with thymic aplasia, persistent hypocalcemia, facial dysmorphism and cardiac defects.

Pseudohypoparathyroidism (Albright hereditary osteo­dystrophy) is characterized by genetically determined decreased responsiveness of PTH receptors, leading to hypocalcemia despite raised PTH levels (d/d true hypoparathyroidism). Most cases present at 7-8 years of age with recurrent tetany and typical somatic features, e.g. brachydactyly with dimpled dorsum of hand and short 4^th metacarpal. Mental retardation, short stature, cataract and basal ganglia calcifications are common.

Hyperparathyroidism, i.e. increased PTH secretion may be primary (parathyroid disease) or secondary (to hypocalcemia due to any cause), the later being inconsequential due to absence of hypercalcemia.

Etiology: Primary hyperparathyroidism is almost always caused by parathyroid tumors, e.g. solitary adenoma or multiple endocrinal neoplasia (type I), except rare cases of ectopic PTH-secreting tumors or neonatal parathyroid hyperplasia.

Clinically, Primary hyperparathyroidism presents with:

• Early hypercalcemia with weight loss, muscular weakness, constipation and polyuria/polydipsia

• Prolonged calciuria leading to nephrocalcinosis, renal calculi and chronic renal failure.

• Increased bone resorption, leading to backache, limb pains, deformities and pathological fractures.

• PTH crisis (S. Ca++ gt;15 mg/dl) presenting as rapidly progressive oliguria and renal failure.

Diagnosis rests on:

• Elevated PTH levels with hypercalcemia.

• X-rays showing typical subperiosteal resorption of bone (in phalanges) apart from rarefaction/ trabeculation/cystic changes in skull and renal calculi/nephrocalcinosis in abdomen.

• Abnormal renal functions with hyposthenuria.

• D/D: Primary hyperparathyroidism must be distin­guished from other causes of hypercalcemia (Ch 7.4) and secondary hyperparathyroidism (with normal/ low calcium levels).

Management of primary hyperparathyroidism is essentially the surgical removal of tumor, followed by calcium and Calcitriol supplementation and correction of deformities.

22.5