Chapter 565 Hypoparathyroidism

Etiology

Hypocalcemia is common between 12 and 72 hr of life, especially in premature infants, in infants with asphyxia, and in infants of diabetic mothers (early neonatal hypocalcemia) (Chapter 100) (Table 565-1). After the 2nd to 3rd day and during the 1st wk of life, the type of feeding also is a determinant of the level of serum calcium (late neonatal hypocalcemia). The role played by the parathyroid glands in these hypocalcemic infants remains to be clarified, although functional immaturity of the parathyroid glands is invoked as one pathogenetic factor. In a group of infants with transient idiopathic hypocalcemia (1-8 wk of age), serum levels of parathyroid hormone (PTH) are significantly lower than those in normal infants. It is possible that the functional immaturity is a manifestation of a delay in development of the enzymes that convert glandular PTH to secreted PTH; other mechanisms are possible.

Table 565-1 ETIOLOGIC CLASSIFICATION OF HYPOCALCEMIA

PARATHYROID HORMONE DEFICIENCY

Suppression of neonatal PTH secretion due to maternal hyperparathyroidism

Preproparathyroid hormone gene mutation

• Autosomal dominant

Ca²⁺-sensing receptor activating mutation

• Sporadic

• Autosomal dominant

Autoimmune parathyroiditis

• Isolated

• With type 1 autoimmune polyendocrinopathy, APECED

Mutation of AIRE gene

Infiltrative lesions

• Hemosiderosis (treatment of thalassemia)

• Copper deposition (Wilson disease)

PARATHYROID HORMONE RECEPTOR DEFECTS (PSEUDOHYPOPARATHYROIDISM)

Type 1a (inactivating mutation of G_sα)

• With gonadotropin-independent precocious puberty

Type 1b (paternal imprinting of GNAS1)

Type 2 (normal cAMP response)

MITOCHONDRIAL DNA MUTATIONS

Kearns-Sayre syndrome

Pearson marrow pancreas syndrome

Mutation of long-chain 3-hydroxyacylcoenzyme A dehydrogenase

MAGNESIUM DEFICIENCY

Renal magnesium loss (autosomal dominant)

Magnesium malabsorption (autosomal recessive)

Aminoglycoside therapy

EXOGENOUS INORGANIC PHOSPHATE EXCESS

Laxatives

Soft drinks with phosphoric acid

VITAMIN D DEFICIENCY

Nutritional

Vitamin D dependency (rickets)

Mutation of 1α-(OH)ase (cytochrome P-450)

APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; cAMP, cyclic adenosine monophosphate; PTH, parathyroid hormone.

Aplasia or Hypoplasia of the Parathyroid Glands

Aplasia or hypoplasia of the parathyroid glands is often associated with the DiGeorge/velocardiofacial syndrome (see Fig. 564-1). This syndrome occurs in 1/4,000 newborns. In 90% of patients, the condition is caused by a deletion of chromosome 22q11.2. Approximately 25% of these patients inherit the chromosomal abnormality from a parent. Neonatal hypocalcemia occurs in 60% of affected patients, but it is transitory in the majority; hypocalcemia can recur or can have its onset later in life. Associated abnormalities of the 3rd and 4th pharyngeal pouches are common; these include conotruncal defects of the heart in 25%, velopharyngeal insufficiency in 32%, cleft palate in 9%, renal anomalies in 35%, and aplasia of the thymus with severe immunodeficiency in 1%. This syndrome has also been reported in a small number of patients with a deletion of chromosome 10p13, in infants of diabetic mothers, and in infants born to mothers treated with retinoic acid for acne early in pregnancy.