ACUTE INTERSTITIAL NEPHRITIS

Acute interstitial nephritis or tubulointerstitial nephritis an inflammatory disorder of predominantly renal inter- stitium due to any cause, is an important cause of acute renal failure though some cases may present with chronic renal insufficiency.

Etiology: Leading causes of acute interstitial nephritis in childhood include—(a) drugs, e.g. NSAIDs, penicillin,

• IGF₁ deficiency (IGF₁ gene or receptor defects)

Genetic causes involve either GH1 or GHRHR gene defects, which may be autosomal recessive, dominant or X-linked recessive.

Clinically, these cases have normal length at birth but intermittent episodes of hypoglycemia are common in neonatal period and infancy.

Most cases present beyond first year of life with—(a) proportionate severe short stature due to lower growth velocity, (b) doll-like appearance due to truncal obesity,

• Neurological problems, e.g. visual field defects, raised ICP, behavioral problems.

Diagnosis depends on: (a) elevated GH levels (usually gt;400 ng/ml), which cannot be suppressed below 5 ng/ ml on glucose suppression test, (b) elevated IGF1 and IGFBP-3 levels, and (c) neuroimaging to delineate the tumor. Levels of other pituitary hormones are often reduced with/without clinical manifestations due to destruction of anterior pituitary by growing adenoma.

D/D includes other causes of tall stature (Ch 3.4), the closest being cerebral gigantism.

Cerebral gigantism (Soto's syndrome) is an unexplained, probably hypothalamic, disorder, characterized by rapid linear growth from birth to 3-4 years of age, macrocrania, intellectual disability, gait abnormalities and normal or precocious puberty. GH levels are essentially normal and unlike pituitary gigantism, bone age is usually delayed.

Management includes removal of adenoma by surgery or irradiation. Octreotide (IM 1-40 #956;g#8725;kg#8725;d)-a synthetic somatostatin analogue is very effective to suppress GH secretion and reduce the tumor size.

Cushing syndrome is the commonest disorder of adrenocortical hyperfunction, characterized by cortisol excess and consequent clinical features, e.g. obesity, growth failure and hypertension, etc.

Etiology: Cushing syndrome is caused by excess endo­genous production of cortisol in adrenal, pituitary or hypothalamic disorders or rarely from ectopic sources, e.g. tumors (Table 22.11). A functioning malignant tumor of adrenal cortex (rarely adenoma) is the commonest cause of Cushing syndrome in infancy and early childhood, while Cushing disease, i.e. bilateral adrenal hyperplasia, due to excessive ACTH secretion from pituitary adenoma, is more common in older cases gt; 6 years.

TABLE 22.11: Causes of Cushing syndrome

• Primary adrenal disease

- Tumors, e.g. carcinoma, adenoma (gt;45%)

- Primary nodular dysplasia

- McCune-Albright syndrome

• Pituitary adenoma (Cushing disease) (50%)

• Hypothalamic tumors (#8593;CRH)

• Ectopic ACTH-secreting tumors* *

• End-organ resistance

• Iatrogenic steroids (cushingoid syndrome) *malignant tumors of bronchus, thymus, pancreas

22.5.5