FIGURE 89.3 Secondary hyperparathyroidism in a 12-year-old girl with chronic pyelonephritis There is moderate subperiosteal erosion on the radial side of the middle phalanges; note a lacy appearance of the periosteum and small-tuft erosion Subperiosteal bone resorption is the most significant radiologic finding in hyperparathyroidism; subperiosteal bone resorption and tuft erosion are seen in both primary and secondary hyperparathyroidism (Courtesy of Soroosh Mahboubi, MD, The Children’s Hospital of Philadelphia.) HYPOPARATHYROIDISM Goal of Treatment Treatment goals for children with hypoparathyroidism include addressing the clinical effects of hypocalcemia and to initiate treatment with vitamin D and calcium CLINICAL PEARLS AND PITFALLS Presents with signs and symptoms of hypocalcemia Hypocalcemic seizures may be difficult to control Calcium infusions must be done slowly to avoid life-threatening arrhythmias Current Evidence Hypoparathyroidism can occur sporadically or be part of a familial syndrome consisting of combinations of several autoimmune diseases (e.g., Addison disease, diabetes mellitus, lymphocytic thyroiditis, pernicious anemia, ovarian failure) It is also associated with thymic aplasia and severe immunologic deficiencies (DiGeorge syndrome) A transient form of hypoparathyroidism, lasting for as long as year, has been reported in some infants Hypoparathyroidism may also result from damage incurred during thyroid surgery or irradiation The lack of PTH, regardless of cause, has several deleterious effects on calcium homeostasis Because PTH has significant effects on 1,25-(OH)2 D3 formation, the absence of PTH is magnified by a consequent reduction in 1,25-(OH)2 D3 The net effect of the lack of PTH (and decreased quantity of vitamin D) is a declining serum level of calcium, primarily caused by decreased intestinal absorption of calcium and decreased renal resorption of calcium Clinical Considerations Clinical Recognition The predominant historical features and clinical manifestations of hypoparathyroidism are the same as those of hypocalcemia Presenting complaints are often related to paresthesias and tetany that result from hypocalcemia General complaints such as bone pain, headaches, fatigue, and insomnia are also common Physical examination findings are generally nonspecific aside from tetany, when present, or the ability to elicit the Chvostek or Trousseau sign Labs abnormalities include elevated phosphorous, low calcium, low calcitriol, and low PTH (see Chapter 100 Renal and Electrolyte Emergencies ) Triage Hypocalcemia should be considered in a child who has neurologic irritability or myoclonus Initial Assessment/H&P Unique historical information that may suggest the diagnosis of hypoparathyroidism includes other family members with autoimmune endocrine disease, recurrent episodes of serious infection in the affected child, and previous thyroid manipulations Most symptoms and signs of hypoparathyroidism are the same as those related to hypocalcemia The particular symptoms and signs found depend on the age at disease onset, the chronicity of the disease, and the presence of other autoimmune or syndromic phenomena Papilledema without hemorrhage may be seen during the initial examination and tends to resolve within several days after the initiation of therapy Lenticular cataracts are common in hypoparathyroidism and are associated with long-standing hypocalcemia of any cause Psychiatric and neurologic disorders occur in association with hypoparathyroidism Subnormal intelligence occurs in about 20% of children with the idiopathic form of hypoparathyroidism and the severity correlates closely with the period of untreated hypocalcemia Dry, scaly skin is a common finding, as is patchy alopecia Psoriasis or mucocutaneous candidiasis may be found on occasion Unusually brittle fingernails and hair are often found Hypoplasia of tooth enamel may be seen if hypoparathyroidism was present at the time of dental development Intestinal malabsorption and steatorrhea have been reported in association with hypoparathyroidism Management/Diagnostic Testing In most cases, the diagnosis of hypoparathyroidism is first considered when low serum calcium is found If an elevated phosphate accompanies low calcium, low or normal serum alkaline phosphate, and normal blood urea nitrogen, hypoparathyroidism is a likely possibility Finding a low or unmeasurable level of PTH in the presence of hypocalcemia and hyperphosphatemia makes the definitive diagnosis Because PTH increases cAMP levels in the urine, the excreted amount of cAMP in the urine is low in patients with hypoparathyroidism and rises briskly with the administration of exogenous PTH The presence of antibodies in other endocrine tissues or organs may help in delineating the cause of the hypoparathyroidism The acute management of hypoparathyroidism is essentially the management of the hypocalcemia (see Chapter 100 Renal and Electrolyte Emergencies ) Magnesium levels must also be checked, as hypomagnesemia is a rare but important etiology of hypocalcemia Longterm management consists of treatment with vitamin D, usually with one of its more active analogs—1,25-(OH)2 D3 (calcitriol) at 0.01 to 0.05 mCg/kg/day Supplemental oral calcium is almost always necessary The goals of long-term therapy are to maintain the serum calcium in the lower range of normal and to avoid both vitamin D toxicity and hypercalcemia A subcutaneous preparation of recombinant PTH is now available, but uncommonly used for the long-term management of hypoparathyroidism given experimental increases in the incidence of osteosarcoma in animal studies Clinical Indications for Discharge or Admission Asymptomatic patients may be treated as outpatients with close follow-up RICKETS Goals of Treatment To initiate vitamin D (and potentially calcium treatment) to normalize serum phosphate and effect positive changes on radiographs To avoid a potentially dangerous drop in calcium with initiation of treatment CLINICAL PEARLS AND PITFALLS Caused by inadequate dietary intake of vitamin D; incidence is decreasing as increased awareness and increased supplementation in food Failure of calcification affects those parts of the skeleton that are growing most rapidly or that are under stress; a clinical diagnosis that is confirmed by radiology Premature infants are at increased risk for the development of rickets Significant hypocalcemia is unusual in rickets Current Evidence Incidence of rickets is falling given increased supplementation of diets however is still seen among certain ethnic groups, premature infants, children with severe malabsorption problems, and patients with serious renal disease Rickets is caused by the failure of mineralization of bone matrix in growing bone resulting from a lack of vitamin D Consequently, unmineralized cartilage is excessive, and bone is soft In addition to inadequate intake of vitamin D, the other causes of rickets are inability to form the active metabolite of vitamin D, excess phosphate excretion, and excess accumulation of acid Vitamin D may be obtained from dietary sources (especially animal fat) or synthesized from cholesterol via a complex pathway requiring the interaction of the precursor molecule with sunlight Further hydroxylation of vitamin D in the liver (25-hydroxylation) and kidney (1alpha-hydroxylation) leads to the formation of the active metabolite 1,25-dihydroxyvitamin D Therefore, failure to form 1,25-(OH)2 D3 may result from inadequate intake of vitamin D or insufficient exposure to sunlight This is a particular problem among ethnic groups that eat small quantities of animal meat and that are extensively clothed when outdoors Because vitamin D is fat soluble, any problem leading to prolonged fat malabsorption can result in rickets Diseases affecting kidney or liver function may also lead to inadequate production of 1,25-(OH)2 D3 An inherited deficiency of the 1-alpha-hydroxylase in the kidney (vitamin D– dependency rickets) is known Certain drugs, such as phenobarbital and phenytoin, affect liver metabolism of vitamin D and can lead to rickets Premature infants are particularly prone to vitamin D deficiency because of their minimal stores of vitamin D and their limited capacity for vitamin D synthesis Phosphate is a critical component of bone formation Excess excretion of phosphate may lead to clinical rickets Conditions that lead to excess phosphate excretion include primary hyperphosphaturia, Lowe syndrome, and Fanconi syndrome Vitamin D–resistant rickets is a misnomer because the primary defect is in the renal tubular resorption of phosphate and not a resistance to vitamin D Both an X-linked recessive and an autosomal-dominant form of phosphate wasting are known Rickets may also occur in conditions leading to chronic acidosis because bone is resorbed to buffer the acid load This condition is seen in patients with distal renal tubular acidosis and may be partially responsible for the rachitic changes associated with Fanconi syndrome Clinical Considerations Clinical Recognition