This book addresses the need for comprehensive review of therapeutic options that are known to be efficacious in the management of cutaneous diseases in children. It summarizes evidence-based literature on clinical responses among pediatric patients, including age-appropriate management strategies. Included is review of the extraordinary developments in understanding of the genetics and pathogenesis of many cutaneous disorders during the past decade, the novel therapeutic options and repurposing of old drugs, and the management of some of the most challenging skin disorders.
Therapy in Pediatric Dermatology: Management of Pediatric Skin Disease is a succinct, user-friendly, and up-to-date therapeutic dermatologic textbook for physicians who care for children with skin disorders. Each skin condition is discussed with investigative and treatment recommendations in mind and provided based on extensive review of the literature. This book will provide unbiased, yet concise, information that is valuable to practitioners who manage pediatric patients in their practices.
Copyrighted Work that you can Claim. Base have books.
Springer International Publishing Language: Diagnosis and Management Infectious Disease and Therapy pdf free by Itzhak Brook This totally revised and updated reference covers the latest advances in the diagnosis and treatment of anaerobic bacterial infections in children-describing the activity of, and current therapies for, infections after trauma; in splenic and liver abscess Therapy of skin diseases [electronic resource]: Responsibility Thomas Krieg, David R. Bickers, Yoshiki Miyachi eds. Physical description xxiii, p. Find it at other libraries via WorldCat Limited preview.
Bibliography Includes bibliographical references and index. Phenotypic variability is another problem with the diagnosis of AHO even among affected individuals in a kindred. Nonspecific physical characteristics include short stature and obesity. Brachydactyly is a more specific criterion and can be diagnosed by physical or radiographic examination.
In AHO, the most commonly shortened bones are the distal phalanx of the thumb and the fourth metacarpal. On a radiograph of a normal hand, a line drawn tangential to the distal ends of the fourth and fifth metacarpals passes distal to the head of the third metacarpal. Heterotopic ossification can also occur, but little is known about the cause. Hypocalcemia, hyperphosphatemia, elevated levels of PTH and normal renal function lead one to be highly suspicious of the diagnosis.
A positive family history lends further support. The biochemical hallmark is failure of bone and kidney to respond adequately to PTH. The classic tests of Ellsworth and Howard and of Chase, Melson, and Aurbach 87 involved administration of to USP units of bovine parathyroid extract with measurements of urinary cyclic AMP and phosphate. The test hormone is now synthetic human PTH After administration of human PTH , normal subjects and patients with hypoparathyroidism display to fold increases in urinary cyclic AMP.
Patients with PHP 1a and 1b have markedly blunted responses. The definitive test for the diagnosis of PHP 1 is the analysis of the Gs-alpha protein levels or sequencing of GNAS1 , which can be done in reference laboratories.
Treatment of hypocalcemia in patients with PHP is the same as for other types of hypoparathyroidism. However, patients with AHO may require specific therapies related to skeletal abnormalities. Ossification of ligaments may also require surgery to relieve neurological problems These subjects have normal serum calcium levels and have no other evidence of hormone resistance. These patients have the same mutant allele that can cause Gs alpha deficiency in other affected family members who have hormone resistance Tissue-specific imprinting of GNAS1 in the proximal tubules of the kidney and in the thyroid gland occurs, for example in this disease, such that the paternal allele if it is non-mutant is silenced and allows for the expression of only one mutant maternal allele of GNAS1 in those tissues, producing the phenotype of hormonal resistance.
Skeletal mineralization of the fetus is due to active calcium transport from the mother across the placenta. At term, the fetus is hypercalcemic relative to the mother and may have suppressed PTH levels. Over the first 4 days of life, PTH levels fall first and then rise to normal adult levels by 2 weeks after birth It is more common in premature infants, infants of diabetic mothers, and infants who have suffered asphyxia. The proportional drop in ionized calcium may be less than the drop in total calcium, so those symptoms may not be manifest.
Hypocalcemia in premature infants is not unusual, but the reason is not understood. One proposal is that an exaggerated rise in calcitonin occurs that provokes hypercalcemia. Other hypotheses include the fact that PTH secretion may be impaired in the premature infant.
Based on the understanding of the molecular basis of skin diseases, this truly A Worldwide Perspective on Therapeutic Approaches and Their Molecular Basis. Therapy of Skin Diseases: A Worldwide Perspective on Therapeutic. Approaches and Their. Molecular Basis. First edition. Berlin, Heidelberg: Springer-Verlag.
Infants of diabetic mothers have an exaggerated postnatal drop in circulating calcium levels, and strict maternal glycemic control during pregnancy reduces the incidence of hypocalcemia in these infants. Between 5 and 10 days of life, "late" neonatal hypocalcemia may result in tetany and seizures. This disorder is more common in full-term infants than in premature infants.
One risk factor is hyperphosphatemia due to administration of cow's milk, which may reflect an inability of the immature kidney to secrete phosphate. Magnesium deficiency may also masquerade as hypocalcemia in an infant. Congenital defects of intestinal magnesium absorption or renal tubular absorption can occur resulting in severe hypocalcemia.
Hyperparathyroidism during pregnancy is unusual but can result in hypocalcemia in the newborn Atrophy of the fetal parathyroid glands can occur during intrauterine life due to the increased calcium delivery to the fetus. The infant's parathyroid glands are not able to respond to the hypocalcemic stimulus after birth and maintain normal serum calcium levels. A typically benign autosomal dominant disorder, familial hypocalciuric hypercalcemia FHH , can paradoxically produce neonatal hypocalcemia.
FHH is usually due to heterozygous inactivating mutations in the Casr. There is a report of an infant with late onset life-threatening hypocalcemia secondary to relative hyperparathyroidism. The hypoparathyroidism was thought to be due to fetal parathyroid suppression secondary to high maternal calcium levels in a mother with FHH due to a heterozygous Casr mutation In patients with chronic illness, malnutrition, cirrhosis, or volume over-expansion, serum albumin may fall with a reduction in the total, but generally not the ionized, fraction of serum calcium.
This is referred to as "factitious" hypocalcemia. Patients do not have any of the signs or symptoms listed above of hypocalcemia. There is a correlation between the extent of hypoalbuminemia and hypocalcemia such that one can calculate the corrected total serum calcium. This is not a completely precise method, and serum ionized calcium measurements can confirm whether true hypocalcemia is present. Hypocalcemia is commonly associated with magnesium depletion.
Hypomagnesemia may be caused by excessive losses through the gastrointestinal tract. Chronic diarrhea of essentially any etiology can cause hypomagnesemia. Non-tropical sprue, radiation therapy, bacterial and viral dysentery, and severe pancreatitis can cause hypomagnesemia. Bypass or resection of the small bowel may also result in intestinal magnesium loss. Mutations in several genes important in magnesium conservation may also cause intestinal magnesium loss 93, Loss of magnesium through renal mechanisms may be due to osmotic diuresis or glycosuria, and it may also occur in hypoparathyroidism.
Many drugs cause renal magnesium wasting such as diuretics, aminoglycosides, amphotericin B, cisplatinum, cyclosporin, and pentamidine 7,8. A rare etiology is primary familial hypomagnesemia, which usually is diagnosed at a very young age. Hypomagnesemia with secondary hypocalcemia, due to a mutation in TRPM6 , was described simultaneously by two groups 95, It is highly similar to TRPM7, a bifunctional protein combining calcium- and magnesium-permeable cation channel activities with protein kinase activity.
TRPM6 is present in both kidney tubules and intestinal epithelia and maps to chromosome 9q. This autosomal recessive disorder can sometimes present with the triad of hypomagnesemia, hypokalemia, and hypocalcemia. It is treatable with life-long magnesium supplementation. Recognition and treatment can prevent long-term neurological defects.
Several other inherited disorders causing hypomagnesemia have been elucidated and are described in recent reviews 93, Patients with severe hypocalcemia due to magnesium depletion should be treated with intravenous magnesium at a dose of 48 mEq over 24 hours. Although magnesium can be administered intramuscularly, these injections are usually painful. Even though intravenous magnesium administration may result in prompt normalization of magnesium levels, hypocalcemia may not be corrected for days. This may be because cellular uptake of magnesium is slow, and magnesium is predominantly an intracellular cation.
Repletion of magnesium thus requires sustained correction of the deficiency state. Magnesium therapy may be continued until the biochemical signs of depletion hypocalcemia and hypokalemia resolve. Hyperphosphatemia can lower serum calcium. There are many causes of hyperphosphatemia, including increased intake of phosphate, decreased excretion of phosphate or increased translocation of phosphate from tissue breakdown into the extracellular fluid. Renal insufficiency is probably the most common cause of hyperphosphatemia. The use of phosphate-containing enemas or zealous use of oral phosphate may also lead to hyperphosphatemia.
Vitamin D administration, especially of vitamin D metabolites like calcitriol, may also cause hyperphosphatemia. The transcellular shift of phosphate from cells into the extracellular fluid compartment is seen in tissue destruction or increased metabolism. Examples of transcellular shifts include changes in phosphate that accompany treatment of acute leukemias or lymphomas or large bulky solid tumors with effective chemotherapy. Rapid release of cellular phosphate may occur causing the tumor lysis syndrome In rhabdomyolysis due to crush injury, hypocalcemia and hyperphosphatemia may occur.
Severe intravascular hemolysis may lead to a similar syndrome. In diabetic ketoacidosis, ketone-induced urinary losses of phosphate deplete total body stores, but patients may present with hyperphosphatemia. When the volume shifts during the correction of hyperglycemia and acidosis, the shift of phosphate back into cells can result in mild transient hypophosphatemia. Hyperphosphatemia alters the calcium-phosphate product and the solubility of these ions. This may lead to calcium salt deposition in soft tissues. Ectopic calcifications in tissues may form, including in blood vessels, heart valves, skin, periarticular tissues, and the cornea band keratopathy.
Hyperphosphatemia inhibits 1-alpha-hydroxylase activity in the kidney. The resulting lower circulating concentrations of 1,25 OH 2 vitamin D may further aggravate the hypocalcemia by impairing intestinal absorption of calcium. Hypocalcemia and tetany may occur if serum phosphate rises rapidly. Treatment should be directed towards reducing the hyperphosphatemia in order to correct the hypocalcemia.
Hyperphosphatemia-induced hypocalcemia inhibits vitamin D bioactivation in the kidney and the resulting low 1,25 OH 2 vitamin D levels may result in increased PTH secretion. Secondary hyperparathyroidism from long-term hyperphosphatemia has been well described and is usually associated with renal insufficiency. Ectopic calcifications in tissues may occur. There are many drugs associated with hypocalcemia.
One class of such agents is inhibitors of bone resorption. These drugs include bisphosphonates, calcitonin, and denosumab, the neutralizing monoclonal antibody to the receptor activator of nuclear factor kappa B ligand RANK-L Calcitonin, given in multiple doses daily is a short-term treatment for hypercalcemia, so hypocalcemia is an expected therapeutic outcome with such a dosing regimen. Hypocalcemia after administration of an intravenous bisphosphonate like pamidronate or zoledronic acid is uncommon but if it occurs can be prolonged 99, This is especially true in patients with underlying vitamin D deficiency.
Patients receiving denosumab for osteoporosis or metastatic cancer to bone are at risk for hypocalcemia, especially if there is underlying chronic kidney disease Oral or parental phosphate preparations can also lower serum calcium. Hypocalcemia and osteomalacia have been described with prolonged therapy with anticonvulsants such as phenytoin diphenylhydantoin or phenobarbital.
Hypocalcemia has also been found in patients undergoing pheresis and plasmapheresis with citrated blood. Fluid overdoses during dialysis, over-fluorinated public water supplies, and ingestion of fluoride-containing cleaning agents have all been associated with low serum calcium levels.
In this case, hypocalcemia is thought to be due to excessive rates of skeletal mineralization secondary to formation of calcium difluoride complexes. Chemotherapeutic agents such as the combined use of 5-fluorouracil and leucovorin, may result in mild hypocalcemia. The hypomagnesemia caused by cisplatinum can induce hypocalcemia. Rapid remineralization of the bone occurring postoperatively, after thyroidectomy for thyrotoxicosis or parathyroidectomy for hyperparathyroidism, is referred to as "hungry bone syndrome" 26,27, It is due to a rapid increase in bone uptake of serum minerals after the removal of a stimulus of high rates of bone remodeling thyroid hormone or PTH.
When the stimulus is removed, there is a dramatic increase in bone formation. Hypocalcemia can occur if the rate of skeletal mineralization exceeds the rate of osteoclast-mediated bone resorption. This syndrome can be associated with severe and diffuse bone pain and tetany. A similar pathophysiology net rapid uptake of calcium into bone is the cause of hypocalcemia due to osteoblastic metastases. This may occur in patients with prostate or breast cancer 7. Acute leukemia or osteosarcoma can also result in hypocalcemia. In patients with vitamin D deficiency and symptoms of osteomalacia, institution of vitamin D therapy can result in hypocalcemia.
All these disease states result in hypocalcemia due to rapid mineralization of large amounts of unmineralized osteoid. Pancreatitis can be associated with lipid abnormalities, hypocalcemia, and even tetany. With the development of animal models, the mechanism of hypocalcemia is known When the pancreas is damaged, free fatty acids are generated by the action of pancreatic lipase.
A recent case of hypoparathyroidism was described in which the affected patient was found to have a homozygous mutation in PTH at residue 25 arginine substituted with cysteine. A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism. Mayo Clin Proc The use of phosphate-containing enemas or zealous use of oral phosphate may also lead to hyperphosphatemia. Rosen ed , John Wiley and Sons, Eighth edition, pp , Addison's disease adrenal insufficiency follows. With twice-daily administration of PTH compared to twice-daily calcitriol for 3 years in 27 patients, Winer et al reported stabilization of serum calcium levels just below the lower limit of normal and a normalization of urinary calcium excretion at the target level of 1.
There are insoluble calcium salts present in the pancreas, and the free fatty acids avidly chelate the salts resulting in calcium deposition in the retroperitoneum. In addition, hypoalbuminemia may be part of the clinical picture so that there is a reduction in total serum calcium. If there is concomitant alcohol abuse, emesis or poor nutrition, hypomagnesemia may augment the problem.
PTH levels can be normal, suppressed or elevated. If PTH levels are normal or suppressed, hypomagnesemia may be present. If PTH levels are elevated, this is a reflection of the hypocalcemia. In the treatment of these patients, parenteral calcium and magnesium replacements are indicated.
Vitamin D status should be assessed to rule out malabsorption or nutritional deficiencies. There are multiple reasons why a patient with acute illness may experience hypocalcemia. Acute or chronic renal failure, hypomagnesemia, hypoalbuminemia "factitious hypocalcemia" , medications, or transfusions with citrated blood may all alter levels of serum calcium. Pancreatitis, as stated above, may also result in hypocalcemia.
Another setting in which hypocalcemia can occur is sepsis and usually confirms a grave prognosis In gram negative sepsis or in the "toxic shock syndrome", there is a reduction in both total and ionized serum calcium. The mechanism of action remains unknown, but elevated levels of the cytokines IL-6 or TNF-alpha may be mediators of hypocalcemia. In a study of patients with acute illnesses, the 3 most common factors identified with low calcium levels were hypomagnesemia, presence of acute renal failure, and transfusions. The level of hypocalcemia correlated with patient mortality To assess the incidence of hypocalcemia in critically ill patients, Zivin and colleagues compared the frequency and degree of hypocalcemia in nonseptic critically ill patients.
Three groups of hospitalized patients were studied: No specific illness renal failure, blood transfusions was associated with hypocalcemia. During surgical procedures, hypocalcemia may occur with the rapid infusion of citrated blood, with physiologic increases in serum PTH levels. Symptoms are variable in this setting, and it is thought that the phenomenon is due to acute hemodilution by physiological saline and complexation of calcium by the large amounts of citrate infused. Hypocalcemia due to hypoparathyroidism is well recognized in transfusion-dependent patients with beta-thalassemia It is thought that hypoparathyroidism and the other endocrinopathies seen in patients with thalassemia are due to iron overload.
Their presence correlates with disease duration and extent of transfusions. The decision to treat is dependent on presenting symptoms, and the severity and rapidity with which hypocalcemia develops. All treatment requires close monitoring. If intravenous infusions are contemplated, hospitalization in an intensive care unit or specialized unit with access to cardiac monitoring and rapid ionized calcium determinations is ideal for optimal management and safety. Acute hypocalcemia can be life-threatening, as patients may present with tetany, seizures, cardiac arrhythmias, laryngeal spasm, or altered mental status.
Calcium gluconate is the preferred intravenous calcium salt as calcium chloride often causes local irritation. This can be repeated until the patient's symptoms have cleared. With persistent hypocalcemia, administration of a calcium gluconate drip over longer periods of time may be necessary. Drip rates of 0. As soon as possible, oral calcium supplementation should be initiated and, if warranted, therapy with vitamin D or its analogues.
Intravenous administration of calcium is not without problems. Rapid administration could result in arrhythmias so intravenous administration should be carefully monitored. If local extravasation into soft tissues occurs, calcifications due to the precipitation of calcium phosphate crystals can occur Calcium phosphate deposition can occur in any organ and is more likely to occur if the calcium-phosphate product exceeds Calcium phosphate deposition in the lungs, kidney or other soft tissue may occur in patients receiving intravenous calcium especially in the presence of high serum phosphate levels.
It is essential to measure serum magnesium in any patient who is hypocalcemic, as correction of hypomagnesemia must occur to overcome PTH resistance before serum calcium will return to normal. In chronic hypocalcemia, patients can often tolerate remarkably severe hypocalcemia and remain asymptomatic. For patients who are asymptomatic or with mildly symptomatic hypocalcemia, calcium homeostasis can be restored with oral calcium and vitamin D or an activated vitamin D metabolite such as calcitriol 7,8.
Oral calcium carbonate is often the most commonly administered salt, although many different calcium salts exist. Oral doses calcium should be in the amount of 1 to 3 grams of elemental calcium in 3 to 4 divided doses with meals to ensure optimal absorption. There are expensive forms of calcium supplements that have relatively few additional advantages.
Liquid calcium supplements are available such as calcium glubionate that contains mg of calcium per 10 mL or liquid forms of calcium carbonate. Calcium phosphate salts should be avoided. The overall goal of therapy is to maintain serum calcium in the low normal range, especially in patients with hypoparathyroidism 7,8, Serum calcium should be tested every 3 to 6 months or when any changes in the medical regimen are made.
One potential side effect of therapy in patients with hypoparathyroidism is hypercalciuria which can be complicated by nephrocalcinosis, nephrolithiasis, and or renal insufficiency. A hour urine calcium along with creatinine determination should be done at least annually, once stable doses of supplements are established.
Serum levels of calcium are poor indicators of the presence of hypercalciuria and nephrocalcinosis The patient should also regularly see an ophthalmologist to screen for cataracts. When treating hypocalcemia in the presence of hyperphosphatemia, special care must be taken sometimes with the use of a phosphate binder to avoid soft tissue calcium phosphate precipitation. Soft tissue calcification can occur in any tissue, but involvement of vital organs such as the lungs, kidney, heart, blood vessels, or brain can result in substantial morbidity or mortality For patients with hypoparathyroidism, vitamin D2 or D3 ergocalciferol or cholecalciferol, respectively or vitamin D metabolites [calcitriol or 1, OH 2 vitamin D or 1 alpha-OH vitamin D not available in the US ] are often required.
Calcitriol, the active metabolite of vitamin D, is rapid-acting and physiologic and is often used for initial therapy. Where rapid dose adjustment is necessary, such as growing children, this may be the most convenient approach Most patients require 0. Among other options, ergocalciferol is a less expensive choice and has a long duration of action. When therapy needs to be administered acutely, calcitriol should be given for the first 3 weeks but then tapered off as the dose of ergocalciferol becomes effective.
If calcitriol is the vitamin D metabolite administered, then the serum 25 OH vitamin D level should be checked periodically to assure that vitamin D sufficiency is maintained. Thiazide diuretics can increase renal calcium reabsorption in patients with hypoparathyroidism. Furosemide and other loop diuretics can depress serum calcium levels and should be avoided.
Other factors that may precipitate hypocalcemia are glucocorticoids since they can antagonize the action of vitamin D and its analogues. Administration or withdrawal of exogenous estrogen can also influence calcium and vitamin D replacement therapy. Estrogen increases calcium absorption at the level of the intestine and indirectly through stimulation of renal 1-alpha-hydroxylase activity. Dose adjustment may be required after changes in estrogen therapy due to alteration in calcium homeostasis.
During the pre- and postpartum period in pregnant patients with hypoparathyroidism, doses of vitamin D often need frequent adjustments. This is due to placental production of 1, OH 2 vitamin D in pregnancy, the increasing levels of PTH-rP from placental, maternal and fetal tissues later in pregnancy, and the high levels of PTH-rP in conjunction with the estrogen-deficient state of lactation How well current treatment strategies calcium salts, vitamin D and its metabolites maintain quality of life in patients with hypoparathyroidism has been assessed to a limited extent In a cross-sectional, controlled study, 25 women with postsurgical hypoparathyroidism on stable calcium and vitamin D treatment were compared to 25 control subjects with a history of thyroid surgery.
Quality of life, urinary calcium excretion and renal calcifications, serum creatinine, and the presence of cataracts by slit lamp examination were assessed. Serum calcium was in the therapeutic target range in 18 of 25 hypoparathyroid patients. Eleven of 25 hypoparathyroid patients had cataracts, and 2 of 25 had renal stones Compared to the control group, those with hypoparathyroidism had higher global complaint scores with predominant increases in anxiety and phobic anxiety subscores and their physical equivalents using validated questionnaires.
Thus, by both physical and psychologic assessments, there were several parameters that were reduced compared to control subjects. The time-weighted average for serum calcium maintained between 7. Just 53 of patients had any hour urine calcium level determined. Analysis of renal function showed rates of chronic kidney disease stage 3 or greater of 2- to fold higher than age-adjusted normal subjects Overall, it was concluded that patients with hypoparathyroidism suffer excess morbidity, especially with regard to renal outcomes.
Underbjerg et al , examined clinical outcomes in a case-control study of Danish patients with hypoparathyroidism compared to age- and gender-matched controls. Patients with postsurgical hypoparathyroidism demonstrated increased risk of renal complications hazard ratio [HR], 3. No increased cardiovascular complications or deaths were seen. Using the same cohort, Underbjerg et al further reported greater risks of hospitalization for infections HR, 1.
Risks of cataracts, cancers, spinal stenosis, and fractures were not increased. The same investigators assessed the epidemiologic features of nonsurgical hypoparathyroidism in Danish patients Based on data from patients collected from to , these investigators found a marked increased in renal insufficiency HR, 6. Neuropsychiatric complications HR, 2. This was thought to be due to the longer duration lifetime of the genetic condition responsible for the nonsurgical hypoparathyroidism in these patients.
In hypoparathyroidism, ideal treatment would theoretically be to replace the hormone itself in a physiologic manner.
In a trial of hypoparathyroid patients, once daily administration of PTH normalized serum and urine calcium levels, but the action lasted only 12 hours With twice-daily administration of PTH compared to twice-daily calcitriol for 3 years in 27 patients, Winer et al reported stabilization of serum calcium levels just below the lower limit of normal and a normalization of urinary calcium excretion at the target level of 1.
Patients on calcitriol in this trial had urinary calcium levels above normal. Serum creatinine levels were stable over time in both groups of patients, and biochemical markers of bone turnover increased with PTH treatment compared to control levels at baseline. BMD by dual energy x-ray absorptiometry DXA increased slightly but significantly at the lumbar spine and whole body in the calcitriol-treated patients and remained stable over 3 years in the PTH-treated group.
These studies in adults , included patients with a variety of different etiologies for their hypoparathyroidism including patients with activating Casr mutations. Two other studies done in children , demonstrated stabilization of serum calcium levels with twice-daily treatment and normalization of urinary calcium excretion on both PTH and calcitriol. The most promising results for lowering urinary calcium into an acceptable range was seen during continuous PTH infusion. Serum calcium, phosphorus, and magnesium concentrations were comparable with the two modes of PTH delivery. These findings suggest that renal PTH receptors may require more continuous exposure to the hormone to reabsorb calcium adequately.
Three recent trials have tested the ability of PTH therapy to permit lowering of calcium and calcitriol supplements safely while maintaining serum calcium homeostasis in patients with chronic hypoparathyroidism Since there was no placebo control group in this study, reports of improved quality of life parameters must be interpreted cautiously. Two other clinical trials, which included placebo treatment arms, further assessed the safety and efficacy of PTH therapy in hypoparathyroid subjects , As serum calcium levels rose, supplements were reduced.
This outcome may have affected the quality of life during the study because no differences were noted between the PTH - and placebo-treated groups in those assessments. In the second randomized, placebo-controlled trial, PTH or placebo was administered for 24 weeks to patients with chronic hypoparathyroidism as calcium supplements and activated vitamin D calcitriol or alphacalcidol were actively down-titrated Urinary calcium levels did not differ substantially between PTH - compared to placebo-treated groups.
Extension studies are in progress from two of these trials , to determine long-term safety and efficacy of PTH in this patient population.