Drugs And Pregnancy Part 7

Cheek TG, Samuels P. Pregnancy-induced hypertension. In: Datta S (ed.). Anesthetic and Obstetric Management of High-Risk Pregnancy, 2nd edn. St Louis: Mosby, 1996: 386411 (Chapter 21).

Groves TD, Corenblum B. Spironolactone therapy during human pregnancy. Am J Obstet Gynecol 1995; 172 172: 1655.

Little BB. Pharmac.o.kinetics during pregnancy. Evidence-based maternal dose formulation.

Obstet Gynecol 1999; 93 93: 85868.

74.Cardiovascular drugs during pregnancy Magee LA, Schick B, Donnenfeld AE et al. The safety of calcium channel blockers in human pregnancy. A prospective, multicenter cohort study. Am J Obstet Gynecol 1996; 174 174: 8238.

Paran E, Holzberg G, Mazor M, Zmora E, Insler V. Beta-adrenergic blocking agents in the treatment of pregnancy-induced hypertension. Int J Clin Pharmacol Therap 1995; 33 33: 119.

Rigo J Jr, Glaz E, Papp Z. Low or high doses of spironolactone for treatment of maternal Bartter's syndrome. Am J Obstet Gynecol 1996; 174 174: 297.

Sanson B-J, Lensing AWA, Prins MH et al. Safety of low-molecular-weight heparin in pregnancy. A systematic review. Thromb Haemost 1999; 81 81: 66872.

Turrentine MA, Braems G, Ramirez MM. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstet Gynecol Surv 1995; 50 50: 534.

Further references are available on the book's website at http://www.drugsandpregnancy.com 4.Endocrine disorders, contraception, and hormone therapy during pregnancy: embryotoxic versus fetal effects Major endocrine disorders 77.Infertility 91.Thyroid gland 80.General hormonal therapy 92.Parathyroid gland 83.Special considerations 98.Pituitary gland 84.Summary 99.Adrenal gland 87.Key references 99.Contraception 89.Complex changes in maternal endocrine systems occur in normal women as a result of the altered metabolic demands of pregnancy. Disorders of endocrinologic systems may be a.s.sociated with adverse maternal, embryonic, or fetal effects. These effects include increases in infertility, spontaneous abortion, fetal malformations, maternal and fetal metabolic derangements, and maternal and fetal death. Certain endocrine disorders, such as gestational diabetes mellitus, arise spontaneously during pregnancy, whereas preexisting endocrine disorders may be exacerbated, may improve, or may remain stable during gestation.

Abnormal fetal growth and development may occur as a result of the disease itself or from the medication(s) used to treat the disease. The teratogenic effects of certain drugs have long been considered a potential hazard for the embryo or fetus, particularly if such agents are administered during the first trimester of pregnancy. Pharmac.o.kinetic behavior of hormones in pregnancy is not well doc.u.mented.

The limited data available indicate that the volume of distribution (V ) increases dur-d ing pregnancy as does clearance for the drugs studied (Table 4.1).

This chapter is designed to address endocrine disorders, hormone therapy during pregnancy, and the possible teratogenic effects of medications. First, it describes briefly the pathogenesis of the major endocrine disorders of pregnancy and second, it enumer-ates the medications that may be used to treat such disorders and their potential embryotoxic and fetal effects.

76.Endocrine disorders, contraception, and hormone therapy during pregnancy Table 4.1 Table 4.1 Pharmac.o.kinetics of endocrine and hormone agents during pregnancy Agent Pharmac.o.kinetics of endocrine and hormone agents during pregnancy Agent n EGA.

Route AUC.

V.

C.

C.

t Cl PPB.

Control Authors d max SS.

1/2.

(weeks) groupa Dexamethasone 6.3340 IV.

Yes (3) Tsuei et al. (1980) Dexamethasone 10.29.PO, IM.

Yes (1) Elliot et al. (1996) Methimazole 7.1239 PO.

Yes (3) Skellern et al. (1980) Oxytocin 9.3740 BU, IV.

Yes (4) Dawood et al. (1980) Source: Little BB. Obstet Gynecol 1999; 93 93: 858.

EGA, estimated gestational age; AUC, area under the curve; V , volume of distribution; C , peak plasma concentration; C , steady-state concentration; t , half-life; Cl, d max SS.

1/2.

clearance; PPB, plasma protein binding; PO, by mouth; denotes a decrease during pregnancy compared to nonpregnant values; denotes an increase during pregnancy compared to nonpregnant values; = denotes no difference between pregnant and nonpregnant values; IV, intravenous; IM, intramuscular.

aControl groups: 1, nonpregnant women; 2, same individuals studied postpartum; 3, historic adult controls (s.e.x not given); 4, adult male controls; 5, adult male and female controls combined.

Major endocrine disorders 77.MAJOR ENDOCRINE DISORDERS.

Diabetes mellitus Diabetes mellitus is a chronic disorder caused by a partial or total lack of insulin. It complicates 0.20.3 percent of all gestations (Connell et al et al., 1985a; Cousins, 1991; Gabbe, 1980; Rodman et al et al., 1976). Clinical manifestations vary with the severity of the disease, and range from an asymptomatic hyperglycemic state to severe diabetic ketoacidosis, coma, and death. Gestational diabetes mellitus is characterized by glucose intolerance arising in the second to third trimesters, and is found in approximately 23 percent of gestations.

Diabetic embryopathy Children of women who have diabetes mellitus prior to pregnancy have a two- to fourfold increase in congenital anomalies compared to the general population (Cousins, 1983, 1987; Mills, 1982). Organ development occurs prior to the 8th week of gestation, and this is the critical window of time during which the teratogenic effect of overt maternal diabetes occurs (Mills et al et al., 1979). Birth defects seen in infants of diabetic mothers involve cardiovascular, skeletal, and central nervous systems (Box 4.1). It is important to note, however, that infants of women who develop gestational diabetes mellitus are not at an increased risk for such defects because the exposure to the disease is outside the critical period of organogenesis (Mills, 1982).

FETAL COMPLICATIONS.

Infants born to women who have diabetes prior to pregnancy and women who acquire gestational diabetes mellitus are at risk for significant neonatal morbidity. These neonates are at increased risk for respiratory distress syndrome, macrosomia, hypoglycemia, hyperbilirubinemia, and hypocalcemia. In addition, the risk of fetal death is Box 4.1 Features of diabetic embryopathy Box 4.1 Features of diabetic embryopathy Cardiovascular Gastrointestinal Coarctation of the aorta Bowel atresias Situs inversus Imperforate a.n.u.s Transposition of great vessels Tracheoesophageal fistula Ventricular septal defect Genitourinary Central nervous system Absent kidneys Hydrocephalus Double ureters Microcephaly Polycystic kidneys Neural tube defects Miscellaneous Skeletal Cleft lip or palate Caudal dysplasia syndrome Polyhydramnios Limb defects Single umbilical artery Adapted from Becerra et al., 1990 and Dignan, 1981.

78.Endocrine disorders, contraception, and hormone therapy during pregnancy two- to three-fold greater than in the general population (O'Sullivan, 1980; Rust two- to three-fold greater than in the general population (O'Sullivan, 1980; Rust et al et al., 1987). Although not conclusive, it is generally accepted that the frequency of these complications can be reduced with good maternal glucose control.

Medications INSULIN.

Insulin is a hormone produced by the beta cells in the pancreas that regulate glucose metabolism and other metabolic processes. Human insulin does not cross the placenta in physiologically significant amounts. Subcutaneous injection is the usual route of administration for insulin, but it can be administered intravenously in an emergency or during a stressful situation where a high degree of control is needed (e.g., labor), to lower the blood glucose rapidly.

Human insulin (semisynthetic or biosynthetic) is preferred over the animal insulins because it is much less antigenic. This is important because maternal insulin antibodies may alter insulin pharmac.o.kinetics and cross the placenta, contributing to fetal hypoglycemia, beta-cell hyperplasia, and hyperinsulinemia (Knip et al et al., 1983). Therefore, most diabetologists agree that immunogenic (animal) insulins should not be used in pregnant women.

Early studies suggested that the human placenta was impermeable to free insulin as well as insulin antibody complexes, but it appears that considerable amounts of antibody-bound animal insulin can cross the placenta. A nonoral drug available to treat diabetes is exenatide, but it has not been studied during pregnancy.

ORAL HYPOGLYCEMIC AGENTS.

The cla.s.ses of oral hypoglycemic drugs include: sulfonureas (acetohexamide, tolazamide, chlorpropamide, tolbutamide, glyburide, glipizide), biguanides (metformin), thia-zolindinediones (rosiglitazone, pioglitazone), and alpha-glucosidase inhibitors (acara-bose or Precose). Oral hypoglycemics are not recommended for use in pregnancy because they are known to cross the placenta and can stimulate fetal insulin secretion.

These drugs have a very long half-life, and administration near term can result in a severely hypoglycemic neonate (Friend, 1981). No epidemiologic studies of birth defects among offspring of women treated with any of these oral hypoglycemic agents have been published.

ACETOHEXAMIDE.

Acetohexamide administration throughout pregnancy has been a.s.sociated with significant neonatal hypoglycemia (Kemball et al et al., 1970). Pregnant rats, given acetohexamide at many times the usual human dose on days 9 and 10, had approximately 50 percent embryonic death, but no abnormalities (Bariljak, 1965). The frequency of congenital anomalies was not increased, other than those expected in diabetes mellitus.

Chlorpropamide is a closely related drug.

CHLORPROPAMIDE.

One out of 41 children born to women treated with chlorpropamide during the first trimester of pregnancy had congenital anomalies, but the malformations were consistent Major endocrine disorders Major endocrine disorders 79.with diabetic embryopathy (Coetzee and Jackson, 1984). It is important to note that neonatal hypoglycemia may occur in infants of diabetic mothers treated with chlorpropamide late in pregnancy (Kemball et al et al., 1970; Zucker and Simon, 1968). Rats treated during pregnancy with chlorpropamide in doses 200 to 300 times those usually employed in humans did not produce congenital anomalies in their offspring (Tuchmann-Duplessis and Mercier-Parot, 1959).

TOLBUTAMIDE.

The frequency of congenital anomalies was not increased among 42 women who were treated with tolbutamide during pregnancy, but only 12 of these women had been treated during the first trimester. Several clinical series have suggested that the frequency of congenital anomalies among infants born to women who took tolbutamide in pregnancy is no greater than would be expected among infants of diabetic mothers (Coetzee and Jackson, 1984; Dolger et al et al., 1969; Notelovitz, 1971). Rat and mouse studies show no increase in congenital anomalies with tolbutamide until the doses are maternally toxic. Tolbutamide does not seem likely to cause birth defects in exposed infants, but this is based on fewer than 50 exposed infants.

TOLAZAMIDE.

There has been one case report of an ear malformation in an infant exposed to the oral hypoglycemic agent tolazamide during the first 12 weeks of gestation (Piacquadio et al et al., 1991). It should be avoided in pregnancy since both tolazamide and tolbutamide will not provide good control in pregnant patients who cannot be controlled by di et al et al one (Friend, 1981). As with other sulfonylurea drugs, neonatal hypoglycemia is likely to occur with chronic use near the time of delivery. one (Friend, 1981). As with other sulfonylurea drugs, neonatal hypoglycemia is likely to occur with chronic use near the time of delivery.

GLYBURIDE.

The transfer rate of glyburide through the human placenta was reported to be much lower than other oral hypoglycemics using in vitro in vitro techniques (Elliott techniques (Elliott et al et al., 1991).

Anencephaly and ventricular septal defect were reported in two infants exposed in utero in utero to glyburide during the first 10 and 23 weeks of gestation, respectively (Piacquardio to glyburide during the first 10 and 23 weeks of gestation, respectively (Piacquardio et et al al., 1991). However, as with all of the agents in this cla.s.s, prolonged neonatal hypoglycemia may be a.s.sociated with maternal therapy (Coetzee and Jackson, 1984). Among more than 180 infants exposed to glyburide during the first trimester, the frequency of congenital anomalies was not increased (Towner et al et al., 1995; Rosa, personal communication, cited in Briggs et al et al., 2002). Given the high background risk for diabetic pregnancies (two- to four-fold higher than the general population), glyburide does not seem to pose a high risk for congenital anomalies.

GLIPIZIDE.

Glipizide is a sulfonylurea drug used to treat noninsulin-dependent diabetes. In one study of 147 infants born to women who took glipizide during embryogenesis the frequency of congenital anomalies was not increased compared to infants born to women who took another sulfonylurea, used insulin, or controlled their diabetes with diet (Towner et al. et al. , 1995). , 1995).

80.Endocrine disorders, contraception, and hormone therapy during pregnancy THYROID GLAND THYROID GLAND Maternal thyroid function changes during pregnancy Thyroxine-binding globulin (TBG) concentrations increase to about twice normal values, resulting in significant elevations in serum L-thyroxine (T4) and liothyronine (T3) concentrations, coupled with a decrease in T3 resin uptake (T3RU) to values in the hypothyroid range (Glinoer et al et al., 1990; Harada et al et al., 1979; Osathanondh et al et al., 1976).

Shortly after delivery, these values return to normal (Yamamoto et al et al., 1979). The concentrations of free T4, free T3, and the free thyroid index (FTI) in maternal serum remain normal throughout gestation (Glinoer et al et al., 1990). Mild diffuse thyromegaly occurs during gestation, probably due to an increased vascularity of the gland, and an increased thyroidal uptake of iodine secondary to elevated renal clearance (Dowling et et al al., 1961; Pochin, 1952). In addition, the placenta produces two hormones with thyroid-stimulating bioactivity. Human chorionic gonadotropin (hCG) and human chorionic thyrotropin (hCT) are secreted in variable amounts, yet are of questionable physiologic impact (Harada et al et al., 1979; Kennedy et al et al., 1992).

Maternal hyperthyroidism Hyperthyroidism occurs in approximately two per 1000 pregnancies (Cheron et al et al., 1981; Mestman, 1980; Selenkow, 1975; Zakarija and McKenzie, 1983). Causes include Graves' disease, Plummer's disease, trophoblastic disease, and Hashimoto's thyroiditis.

Symptoms include heat intolerance, tachycardia, tremulousness, palpitations, agitation, hyperreflexia, exophthalmos, lid lag, and weight loss, but many of these conditions are also seen during a normal pregnancy.

Thyroid hormones do not cross the placenta in significant amounts, but the maternal hyperthyroid state may be dangerous to the fetus and newborn. The incidence of prematurity, preeclampsia, and low birth weight is higher among hyperthyroid gravidas, and maternal weight loss can result in fetal undernutrition (Freedberg et al et al., 1957; Javert, 1940). Thyroid-stimulating immunoglobulins (TSI) can cross the placenta and produce fetal and/or neonatal thyrotoxicosis (McKenzie, 1964). This condition is typically transient and may last from 1 to 3 months in the neonate, until maternal TSI is finally cleared from the infant's serum. However, neonatal syndromes have been described for the transplacental pa.s.sage of both blocking and stimulating antibodies (Zakarija et al et al., 1986).

Treatment of hyperthyroidism during pregnancy involves a choice between ant.i.thyroid drugs and subtotal thyroidectomy since maternal radioiodine treatment results in fetal thyroid ablation (Selenkow et al et al., 1975). Ant.i.thyroid drugs are commonly employed to control hyperthyroidism in pregnancy to avoid surgical intervention.

Medications for hyperthyroidism PROPYLTHIOURACIL.

Propylthiouracil (PTU), a thioamide, is the drug of choice in the therapy of thyrotoxicosis in pregnancy. Its ant.i.thyroid action blocks the synthesis but not the release of thyroid hormone and prevents the peripheral conversion of T4 to T3. Data suggest that Thyroid gland Thyroid gland 81.pregnancy does not have a major effect on the pharmac.o.kinetic disposition of PTU (Sitar et al et al., 1982). PTU crosses the placenta (Marchant et al et al., 1977). The fetus may attempt to compensate for the PTU-induced hypothyroidism, but this is infrequent (15 percent). The drug is not a.s.sociated with an increased risk of congenital anomalies (Becks and Burrow, 1991; Davis et al et al., 1989; Masiukiewicz and Burrow, 1999). Finally, maternal PTU administration has been used with some success to treat congenital fetal hyperthyroidism caused by increases in maternal thyroid-stimulating immunoglobulins (Check et al et al., 1982; Serup and Petersen, 1977). Long-term follow-up of children exposed to PTU in utero in utero revealed no difference in postnatal intellectual and physical development compared with nonexposed siblings (Burrow revealed no difference in postnatal intellectual and physical development compared with nonexposed siblings (Burrow et al et al., 1968, 1978). In summary, PTU is the drug of choice for treating hyperthyroidism in pregnancy, although it can lead to fetal goiter formation in a small number of cases (5 percent or fewer).

METHIMAZOLE AND CARBIMAZOLE.

Methimazole (a thioamide) and carbimazole (a thioamide metabolized to methimazole) are not recommended for use during pregnancy, but should be considered if other medications are not efficacious. Their ant.i.thyroid action blocks the synthesis, but not the release, of thyroid hormone.

Methimazole crosses the placenta (Marchant et al et al., 1977). Fourteen cases of aplasia cutis (scalp defect) among infants exposed to methimazole in utero in utero are described in the literature (Bachrach and Burrow, 1984; Farine are described in the literature (Bachrach and Burrow, 1984; Farine et al et al., 1988; Kalb and Grossman, 1986; Milham, 1985; Milham and Elledge, 1972; Mujtaba and Burrow, 1975). The scalp, skull, and underlying cerebral cortex development is complete by the 3rd month of gestation, suggesting that first-trimester exposure to methimazole is critical for induction of the scalp defects (Kokich et al et al., 1982). However, in the largest series of cases reported (243 infants) of methimazole use in pregnancy, no relationship was found between maternal methimazole therapy and scalp malformations (Momotani et al et al., 1984). It is possible that the a.s.sociation of maternal use of methimazole and carbimazole during pregnancy with congenital skin defects in children is not as strong as originally thought (Van Dijke et al et al., 1987). Two cases of fetal goiter development were reported in a.s.sociation with carbimazole use in pregnancy (Sugrue and Drury, 1980). Follow-up of children exposed to carbimazole in utero in utero found no physical growth or development deficits (McCarroll found no physical growth or development deficits (McCarroll et al et al., 1976). Maternal carbimazole or methimazole therapy for hyperthyroidism is not recommended for use during pregnancy.

ETHIONAMIDE.

Maternal ethionamide administration during pregnancy is known to suppress fetal thyroid hormone synthesis and to result in fetal hypothyroidism and goiter. Based on very limited information, ethionamide (thioamide) does appear to pose a high risk of congenital anomalies (Zierski, 1966).

PROPRANOLOL.

Propranolol is a beta-adrenergic blocker medication that has been used in pregnancy for a variety of indications. The two most common disorders of pregnancy for which propranolol has been used are hypertension and hyperthyroidism. An extensive review of the use of propranolol in pregnancy can be found in Chapter 3.

82.Endocrine disorders, contraception, and hormone therapy during pregnancy IODIDE (POTa.s.sIUM IODIDE) IODIDE (POTa.s.sIUM IODIDE) Iodide compounds are contraindicated for use during pregnancy. Iodides cross the placenta, and the fetus is particularly sensitive to the inhibitory effects of excessive iodide (Wolff, 1969). More than 400 cases of neonatal goiter have been reported in infants of mothers treated with pota.s.sium iodide during pregnancy (Ayromlooi, 1972; Carswell et et al al., 1970; Galina et al et al., 1962; Mehta et al et al., 1983; Miyagawa, 1973; Parmelee et al et al., 1940). These goiters, due to fetal thyroid inhibition with secondary compensatory hypertrophy, can be very large and in some cases lead to tracheal compression and neonatal death.

Only in one scenario is pota.s.sium iodide not only useful, but is indicated during pregnancy the case of 'thyroid storm.' Treatment of this ent.i.ty is acute administration of 1 g of pota.s.sium iodide orally with 1 g of propylthiouracil.

RADIOIODINE (IODINE 131I).

This isotope of iodine is contraindicated for use during pregnancy. One survey of 182 pregnancies inadvertently exposed to radioiodine therapy for hyperthyroidism in the first trimester revealed six infants with hypothyroidism; of these, four were mentally r.e.t.a.r.ded (Stoffer and Hamburger, 1976). A number of case reports doc.u.ment children who developed either congenital or late-onset hypothyroidism after their mothers were treated with 131I during various stages of pregnancy (Fisher et al et al., 1963; Goh, 1981; Green et al et al., 1971; Hamill et al et al., 1961; Jafek et al et al., 1974; Russel et al et al., 1957).

Maternal hypothyroidism Untreated hypothyroidism can impair fertility and increase the incidence of spontaneous abortion, stillbirth, and congenital anomalies (Davis et al et al., 1988; Mestman, 1980; Montoro et al et al., 1981; Pekonen et al et al., 1984). Possible causes of hypothyroidism include iodine deficiency, iatrogenic (thyroidectomy or 131I therapy) or thyroiditis. Symptoms include cold intolerance, irritability, difficulty with concentration, dry skin, coa.r.s.e hair, and constipation. Clinical diagnosis may be difficult because many of these symptoms are commonly seen in normal pregnancy. The mechanism by which maternal hypothyroidism affects the fetus is unknown. Several reports suggest that it is not a major cause of concern (Kennedy and Montgomery, 1978; Montoro et al et al., 1981), but others have reported a high prevalence of congenital malformations and impaired mental and somatic development among the offspring of hypothyroid women (Pharoah et al et al., 1971; Potter, 1980).

Medications for hypothyroidism LEVOTHYROXINE (L-THYROXINE).

L-Thyroxine (T4) is a hormone normally produced in the thyroid gland. It is used to treat thyroid deficiency and is suitable for use during pregnancy. The frequency of congenital anomalies was not increased among 537 pregnancies exposed to exogenous thyroxine or thyroid hormone during the first trimester, and 1605 pregnancies exposed at any time during pregnancy (Heinonen et al et al., 1977a). Experimental studies agreed with the findings in humans. Thyroxine should be considered safe for use during pregnancy.

Parathyroid gland 83.LIOTHYRONINE.

Liothyronine (T3) is a hormone normally produced in the thyroid gland, which is used to treat thyroid deficiency states and is suitable for use during pregnancy. Evidence indicates no increased risk of congenital anomalies in infants whose mothers used liothyronine during pregnancy (Heinonen et al et al., 1977a) (see Levothyroxine).

PARATHYROID GLAND.

Maternal parathyroid function Parathyroid glands, usually four in number, are located along the posterior border of the thyroid gland, and function primarily in the regulation of bone mineral metabolism.

They secrete parathyroid hormone (PTH), which serves to maintain extracellular fluid calcium concentration. Pregnant women require three to four times the nonpregnant daily requirement for calcium, particularly during the latter half of gestation when most of the fetal bone mineral is deposited. Active transfer of calcium and phosphorus across the placenta results in lowering of maternal serum calcium concentration, an increase in PTH secretion, and a reduced calcitonin production (Schedewie and Fisher, 1980).

Maternal 1,25 dihydroxy vitamin D levels and intestinal absorption of calcium increase markedly (Bouillon and Van a.s.sche, 1982; Heany and Skillman, 1971; k.u.mar et al et al., 1979).

Maternal hyperparathyroidism Secretion of excess parathyroid hormone during pregnancy causes increased bone resorption and serum calcium, and other clinical manifestations similar to those in the nonpregnant state. Gravidas may seem asymptomatic; however, 80 percent present with generalized muscle weakness, nausea, vomiting, pain, renal colic, and/or polyuria. Primary hyperparathyroidism is most frequently caused by an adenoma in one of the inferior parathyroid glands. An unusually high frequency of hyperparathyroidism was reported among women with a history of irradiation to the head or neck in childhood (Gelister et al et al., 1989; van der Spuy and Jacobs, 1984). Maternal effects include an increased incidence of renal stone formation caused by hypercalciuria, hyperphosphaturia, and thinning of bone tra-beculae, secondary to increased bone resorption (Peac.o.c.k., 1978; Stanbury et al et al., 1972).

Embryo and fetal effects include a high incidence of spontaneous abortion, stillbirth, neonatal death, and low birth weight (Delmonico et al et al., 1976; Johnstone et al et al., 1972; Kristofferson et al et al., 1985; Ludwig, 1962; Mestman, 1980; Wagner et al et al., 1964). The incidence of severe hypocalcemia and tetany in infants born to mothers with hyperparathyroidism approaches 50 percent (Butler et al et al., 1973; Mestman, 1980; Pederon and Permin, 1975), and is caused by elevated maternal ionized calcium crossing the placenta (active transport) and blunting, ultimately suppressing the fetal parathyroid. Infants are usually unable to maintain normal serum calcium concentration in the perinatal period. Neonatal calcium supplementation is needed, but this effect is transient and usually resolves by 2 weeks of age without sequelae (Pederon and Permin, 1975).

Treatment of choice for primary hyperparathyroidism during the pregnant or nonpregnant state is surgery to avoid maternal, fetal, and perinatal complications.

84.Endocrine disorders, contraception, and hormone therapy during pregnancy Maternal hypoparathyroidism Maternal hypoparathyroidism Hypoparathyroidism is characterized by inadequate PTH, presenting as severe hypocalcemia. Symptoms are similar to the nonpregnant state, including weakness, fatigue, tetany (by Chvostek's and Trousseau's tests) and seizures. The etiology is usually idiopathic, autoimmune or iatrogenic (parathyroid glands removed or blood supply compromised during thyroid surgery). In contrast, pseudohypoparathyroidism is caused by deficient end-organ response to the endogenous PTH. Fetal effects of maternal hypoparathyroidism vary. Untreated maternal hypoparathyroidism is a.s.sociated with neonatal hyperparathyroidism, hypercalcemia, and osteomalacia (Aceto et al et al., 1966; Bronsky et al et al., 1970; Goloboff and Ezrin, 1969; Landing and Kamos.h.i.ta, 1970).