The pituitary enlarges throughout pregnancy, approximately 136% overall,1 and may become hyperintense on scan.2 This enlargement is due primarily to estrogen-stimulated hypertrophy and hyperplasia of the lactotrophs.3 Gonadotrophs decline in number, and corticotrophs and thyrotrophs remain constant.4 Somatotrophs are generally suppressed, and may function as lactotrophs.5 The peak pituitary size is seen in the first 3 days postpartum, when the gland height may reach 12 mm on MRI.1,6,7 The gland involutes rapidly following delivery regardless of breast feeding status, and is of normal size by 6 months postpartum.6,7

Prolactin (PRL) is secreted by the pituitary, hypothalamus, lymphocytes, uterus, placenta, and lactating mammary gland.8 In combination with other hormones, PRL mediates mammogenesis, lactogenesis, galactopoiesis (maintenance of milk secretion), and plays a role in the regulation of humoral and cellular immune responses. Placental estrogens stimulate lactotrophic PRL synthesis in the first trimester,9,10 while progesterone also stimulates prolactin secretion.11,12 Prolactin levels progressively increase approximately 10-fold throughout gestation,13 then decline postpartum in non-lactating women. Despite increased PRL levels, the normal lactotroph continues to respond to TRH and anti-dopaminergic stimulation. Postpartum, the circadian rhythm of PRL release is enhanced by the effects of suckling.

The placental growth hormone (GH) variant differs from pituitary GH by 13 amino acids and is synthesized by the syncytiotrophoblastic epithelium of the placenta. The regulation of placental GH secretion remains unknown, but this variant increases throughout gestation to levels of 10-20 ng/ml.14,15 This variant has similar carbohydrate, lipid,16 and somatogenic properties as pituitary GH, with less lactogenic activity.17 With this increase in overall GH activity, insulin-like growth factor 1 (IGF-1) levels increase in the second half of pregnancy,18 contributing to the acromegaloid features of some pregnant women. Through negative feedback, pituitary GH levels consequently decline in the second half of gestation and the first week postpartum,14,15 with blunted response to hypoglycemic stimulation testing (not recommended in pregnancy), but normal response to GHRH.19 Patients with acromegaly have autonomous pituitary GH secretion, and both forms of GH persist in the blood throughout pregnancy.20

There is a transient fall in TSH in the first trimester during the 2nd and 3rd months. This is postulated to be secondary to human chorionic gonadotropin (hCG) stimulation of the thyroid due to the structural homology between the TSH and hCG molecules and their receptors.21 The role of hCG in increasing thyroid stimulating activity was first postulated with the thyrotoxicosis noted in molar pregnancies and trophoblastic disease,22 with cure after surgical excision of the mole or neoplasm. A negative correlation was later demonstrated between hCG and TSH in women undergoing elective abortion.23 Sequential TSH determinations between 8 and 14 weeks gestation revealed that the nadir in TSH coincides with the peak in hCG,24 with an inverse correlation found in individual samples such that TSH levels fall in a proportional and mirror response to the rise in hCG.(Figure 1)25 There is also a linear relationship between hCG and free T4 concentrations early in gestation.24 In the majority of patients, this effect is transient and not clinically significant, as the peak of hCG is brief. However, sequential evaluations of TSH in a large cohort of pregnant women revealed that 18% demonstrated transient subnormal TSH in the 1st trimester, with 5% still subnormal in the 2nd trimester, with significantly higher levels of hCG found in these women than in those who maintained a normal TSH.26 Furthermore, in hyperplacentosis27 and in twin pregnancies where the hCG peak is generally higher and of longer duration, there is more frequent and greater lowering of TSH than in singleton pregnancies.28 In the second half of gestation, TSH levels return to normal prepregnant levels. In iodine deficient regions, TSH increases near term but remains within the normal range.24 TSH demonstrates an increased response to TRH during gestation. The increase in estrogens produced by the fetal-placental unit stimulates hepatic production of thyroxine-binding globulin and increases the sialylation of the TBG, thereby prolonging its half-life.29,30 This increase in TBG results in higher levels of total T4 and T3, starting at 4-6 weeks gestation.30 Free T4 levels may increase transiently in the 1st trimester as a result of the hCG peak. However, both free T4 and free T3 generally remain within the normal range throughout gestation,24,29,30 though they may be 10-15% lower at term in iodine-sufficient women. Placental deiodination increases maternal T4 turnover.

Synthesis of hCG by syncytiotrophoblasts is itself partially stimulated by placental cytotrophoblast produced gonadotropin releasing hormone (GnRH). In response to placental sex steroid production, both hypothalamic GnRH and pituitary gonadotropin (FSH/LH) levels decline in the first trimester of pregnancy, with a blunted gonadotropin response to GnRH.31 FSH levels are initially suppressed postpartum, and return to normal by 3 weeks postpartum. LH levels tend to normalize more gradually.

Corticotropin-releasing hormone (CRH) levels, synthesized primarily by the placental cytotrophoblasts and the decidua, rise several hundred fold by term.32,33 It stimulates both syncytotrophoblastic placental and pituitary adrenocorticotropic hormone (ACTH) production.34 ACTH levels consequently increase throughout gestation, with a further increase in labor.35 The proportion of ACTH of pituitary vs. placental origin is unknown, however placental ACTH is not suppressible by dexamethasone administration. Cortisol levels progressively increase throughout gestation with a surge during labor.35 Cortisol binding globulin levels rise secondary to estrogen-stimulated production, leading to an increase in total cortisol of 2-3 fold by term.36 The “free” cortisol also rises 3-fold, with a 2-3 fold elevation in urinary free cortisol.35,36

Pituitary adenomas constitute 6.1% of primary intracranial (malignant and nonmalignant) neoplasms in women, with an age-adjusted incidence rate of 0.93 cases/100,000 person-years.37 The stimulatory effect of pregnancy on pituitary lactotrophs will impact a patient with a prolactinoma who becomes pregnant.

Hyperprolactinemia causes one third of all female infertility.38,39 It inhibits pulsatile gonadotropin secretion and the positive feedback of estrogen on gonadotropin secretion.39 Hyperprolactinemia has multiple potential etiologies. In patients with prolactinomas, treatment choices are defined by the clinical presentation and the therapeutic goal.

Surgical therapy is initially curative in approximately 70-80% of patients with microadenomas and rarely causes hypopituitarism. The curative rate is much lower (30%) in patients with macroadenomas, and the risk of hypopituitarism and subsequent infertility increases dramatically.39 For both microadenomas and macroadenomas there is a recurrence rate of about 20%, therby lowering these long-term cure rates.39

Dopamine agonists are the primary therapy for the majority of patients with prolactinoma. Bromocriptine, pergolide (approved for the treatment of Parkinson’s but not prolactinoma), and quinagolide (not approved in the United States) restore ovulatory menses in 70-80% of patients. Approximately 50-75% of patients with macroadenomas experience a > 50% reduction in size.39,40 Cabergoline is dosed once to twice weekly and is more effective and better tolerated than bromocriptine therapy with restoration of ovulatory menses in >90% of women,41 and >90% reduction in tumor size.39,42-45 To establish the intermenstrual interval prior to a pregnancy, mechanical contraception should be used for 2-3 cycles. This allows early recognition of a pregnancy so that the drugs are given for only 3-4 weeks of gestation. The long half-life of cabergoline causes fetal exposure for a further 1 or more weeks after cessation of therapy. Bromocryptine and cabergoline are approved for use in pregnancy, but not pergolide or quinagolide, and caution is certainly advised.

The hormonal milieu of pregnancy may cause significant tumor enlargement in women with prolactin-secreting macroadenomas.(Figure 2) A review of published reports of pregnant patients with microadenomas previously treated with bromocriptine showed that only 12 of 457 (2.6%) pregnancies in women with microadenomas were complicated by symptoms of tumor enlargement (headaches and/or visual disturbances) (Table 1). Surgical intervention was not required in a single case but medical therapy with bromocriptine was instituted in 5 individuals. For patients with macroadenomas, 45 of 142 pregnancies (31%) were complicated by symptoms of tumor enlargement. Surgical intervention was undertaken in twelve of these cases and bromocriptine in 17. In addition, 140 women with macroadenomas were identified who had undergone surgery or radiation prior to pregnancy and their risk of tumor enlargement was 2.5%.46 Reinstitution of bromocriptine or cabergoline therapy generally is successful in reducing tumor size, though transsphenoidal surgery may be required.47,48

Bromocriptine crosses the placenta,49 and continuous administration throughout gestation is not recommended. Experience with its use during the first few weeks of gestation has not been associated with increased risk for adverse events such as spontaneous abortion, ectopic pregnancies, multiple gestation, or congenital anomalies.(Table 2)47,50 Long-term studies of children exposed during the early first trimester have been limited to 64 children ranging in age from 6 months to 9 years, with no ill effects seen.51 In more than 100 pregnancies in which bromocriptine was used throughout gestation, the only neonatal abnormalities noted were a case of undescended testicle and one case of talipes deformity, which is in the expected range.47,50

There are few data on pergolide safety in pregnancy. It is known to cross the placenta in mice, with no teratogenicity noted in doses of 60 mg/kg/day.52 In one patient treated with pergolide in early gestation for Parkinson’s disease, no teratogenic or developmental abnormalities were noted in the offspring.53 However, the authors mentioned 2 major and 3 minor congenital anomalies in 38 pregnancies exposed to pergolide in premarketing studies, with causality not established.53 The manufacturer, Eli Lilly & Co., has limited data on pregnancies in which the fetus was exposed to pergolide. There was no information on 43.4% of pregnancies, 7.2% of pregnancies ended in spontaneous abortion, 7.2% had minor malformations, 14.3% underwent intentional abortions, and 28.6% delivered healthy infants.54 Alternatives to pergolide therapy should be found for women desiring pregnancy.

Quinagolide should not be used when pregnancy is desired. A review of 176 pregnancies in which quinagolide was maintained for a median of 37 days, reported 13.6% spontaneous abortions, 0.6% ectopic pregnancies, 0.6% stillbirths at 31 weeks, and 5.1% malformations: spina bifida, trisomy 13, Down syndrome, talipes, cleft lip, arrhinencephaly, and Zellweger syndrome.55

Cabergoline has been utilized in the first trimester in more than 350 human pregnancies. To date, there is no evidence for increased risk of spontaneous abortion, congenital anomalies, multiple gestation, or premature delivery.56-61 Normal physical and mental development was seen in 107 infants followed 1-72 months.56

There is little specific data regarding the use of transsphenoidal surgery during pregnancy. It is presumed that the risks would be similar to other forms of surgery, except for the increased risk of hypopituitarism.

For patients with intrasellar tumors, bromocriptine or cabergoline therapy is preferred as it is safe for the fetus if it is discontinued early in gestation. These tumors demonstrate a small risk for tumor enlargement. Patients should be followed on a trimester basis for symptomatic enlargement, such as headaches or visual problems. Visual field testing should be performed if clinically indicated.

Therapeutic options for tumors extending outside the sella include prepregnancy surgical debulking, intensive monitoring without dopamine agonist therapy, or continuous bromocriptine therapy throughout gestation. The latter is not likely to harm the fetus but the number of cases followed in this way is small. Patients require monthly assessments and visual field examinations every trimester. Prolactin levels provide little benefit in the clinical assessment, as they may not rise with tumor enlargement.62 With evidence of tumoral enlargement, bromocriptine should be immediately reinstituted and the dose rapidly titrated as tolerated. Switching to cabergoline therapy, transsphenoidal surgery, or delivery if gestation length is adequate, should be considered if the response to bromocriptine therapy is inadequate.47

Breastfeeding stimulates prolactin secretion in normal women in the first few weeks or months postpartum.39 However, there is no evidence that suckling stimulates prolactinoma growth. Therefore, we do not discourage breastfeeding in women with prolactinomas. However, dopamine agonists must be withheld until the period of breastfeeding is over.

Anovulation secondary to hyperprolactinemia in untreated women is associated with hypoestrogenemia and a potential for osteoporosis.39 Although the estrogen in oral contraceptives stimulates lactotrophs and mild increases in prolactin levels in normal women, it does not usually cause growth of microadenomas or precipitate neoplastic development in women with idiopathic hyperprolactinemia.63 Prolactin levels should be evaluated periodically to find the rare estrogen-sensitive tumor. If prolactin levels are found to increase substantially, the estrogen should be stopped to forestall tumor growth. For patients with macroadenomas, dopamine agonists are preferred because of their efficacy in reducing tumor size.

Infertilily is common in women with acromegaly, as approximately 75% of acromegalic women of child-bearing years have menstrual irregularity.64 The ovarian dysfunction is often the result of the hyperprolactinemia found in 30-40% of cases65 and to possible mass effects of the tumor. An additional factor is the coexisting polycystic ovary disease seen in a number of patients.66 Many patients require bromocriptine to ovulate and conceive, and normalization of the hyperprolactinemia frequently restores menstruation. GH and IGF-1 also regulate ovarian function, as GH increases ovarian responsiveness to gonadotropins67 either directly or through IGF-1 production in the ovarian follicle.68

Pituitary growth hormone secretion is autonomous in acromegaly, so both pituitary and placental GH variants persist throughout pregnancy.69 Diagnosing acromegaly during gestation may be difficult as conventional assays are unable to distinguish between the 2 forms of GH. This distinction requires special assays with antibodies which recognize specific epitopes on the pituitary and placental GH variants.14 However, pituitary growth hormone secretion in acromegaly demonstrates a pulsatility of 13-19 pulses per 24 hours,70 vs. the tonic secretion seen with the placental variant.15 In addition, paradoxical GH release after TRH occurs with pituitary GH excess,65 and is not seen with the placental variant.69 Postpartum, the placental variant disappears from the circulation within 24 hours.14 IGF-1 levels are not useful in the diagnosis of acromegaly in pregnancy, as they elevate in the second half of both normal and acromegalic pregnancies.71

Pregnancy was thought to exacerbate the underlying condition in 4 of 24 (17%) pregnant patients with acromegaly who have been described in the literature.72 Tumor enlargement during pregnancy has been described in 2 patients with acromegaly, leading to a visual field defect in one.73,74 Symptomatic tumor enlargement should be monitored monthly, with visual field testing every trimester. Glucose tolerance, hypertension, and cardiac derangements also require monitoring.65 Glucose intolerance occurs in 50% of patients with acromegaly, with overt diabetes mellitus in 10-20%.65 The risk for gestational diabetes mellitus is consequently increased by the insulin resistance of acromegaly. Sodium retention leads to hypertension in 25-35% of patients, with potential for exacerbation in pregnancy. Cardiac disease is present in one third of patients with acromegaly, with underlying cardiomyopathy and increased risk for coronary artery disease, which may also be exacerbated during pregnancy.65,75

GH does not cross the placenta, and maternal acromegaly has little direct impact on the fetus. Fetal somatic growth is largely GH-independent, and macrosomia in such pregnancies is likely secondary to maternal glucose intolerance.

Bromocriptine and cabergoline therapy may provide limited benefit in treating individuals with acromegaly, with no reduction in tumor size and rare normalization of GH levels. Their use in pregnancy has been described above. Neither dopamine agonist should be continued throughout pregnancy in most patients. Somatostatin analogs can cross the placenta. Ten cases have been described of women with acromegaly treated with octreotide during pregnancy,75-77 two cases with acromegaly treated with lanreotide,78,79 one with a TSH-secreting tumor treated with octreotide during pregnancy,80 and one with nesidioblastosis treated with octreotide during pregnancy.81 In most cases the somatostatin analog was stopped before the end of the first trimester, but in two cases octreotide was given throughout the pregnancy.75,81 No malformations were noted. However, octreotide crosses the placenta and somatostatin receptors are widespread in many tissues including the brain; therefore, there certainly is the potential for somatostatin analogs to affect developing fetal tissues.82 Octreotide and lanreotide are not approved for use in pregnancy. Interruption of medical therapy for 9-12 months should have limited impact on the long-term outcome of patients with acromegaly. For enlarging tumors, reintroduction of somatostatin analogs vs. surgery should be considered.

The ACTH-secreting neoplasms will be described in the adrenal disorders section.

There are few data regarding gonadotropin-secreting or TSH-secreting pituitary adenomas in pregnancy. Treatment of three cases of TSH-secreting adenomas has been reported.80,83-85 Octreotide was used in two cases. In one octretide was continued to control tumor size, and the second it was reinstituted to control tumor size. The hyperthyroidism may be controlled with standard antithyroid drug therapy.84

Clinically non-functioning adenomas are primarily gonadotroph adenomas.86 Although unlikely to enlarge under the influence of estrogen stimulation in pregnancy, the lactotroph hyperplasia which occurs can cause chiasmal compression or headaches in a patient with a preexisting clinically non-functioning adenoma. Two cases have been reported of tumor enlargement in pregnancy with resulting visual field defect.73,87,88 In one case, the patient responded to bromocriptine therapy which reduced the lactotroph hyperplasia and had little or no direct effect on the neoplasm.88 Two patients with gonadotroph adenomas secreting intact follicle-stimulating hormone developed ovarian hyperstimulation syndrome.89,90 Pregnancy occurred in both, after bromocriptine therapy in one89 and surgery in the second.90

Hypopituitarism, secondary to neoplastic, vascular, traumatic, or infiltrative disorders, is commonly associated with gonadotropin deficiency and infertility. Fertility is possible with the assistance of the reproductive endocrinologist, using human chorionic gonadotropin and follicle-stimulating hormone, pulsatile GnRH, and in vitro fertilization. During gestation, adrenal and thyroid hormones should be replaced as needed. The average increase in levothyroxine required during gestation is 0.05 mg/day. Adrenal hormone replacement in pregnancy is discussed below.

Hypopituitarism may also present during pregnancy or postpartum, secondary to adenoma expansion, lymphocytic hypophysitis, and pituitary infarction. Recognition may be difficult because fatigue, nausea, and vomiting are frequent accompaniments of normal pregnancies. Dynamic testing during pregnancy is also difficult to interpret in light of the physiologic changes during normal pregnancy. Inadequately treated hypopituitarism may lead to poor pregnancy outcome, including spontaneous abortion, intrauterine fetal demise, maternal hypotension, hypoglycemia, and even maternal death.

Sheehan’s syndrome consists of pituitary necrosis secondary to ischemia occurring within hours of delivery.91,92 It is usually secondary to hypotension and shock from an obstetric hemorrhage. Pituitary enlargement during pregnancy apparently predisposes to the risk for ischemia with occlusive spasm of the arteries to the anterior pituitary and stalk.91,92 The degree of ischemia and necrosis dictates the subsequent patient course. It rarely occurs with current obstetric practice.93

Acute necrosis is suspected in the setting of an obstetric hemorrhage where hypotension and tachycardia persist following adequate replacement of blood products.(Table 1) In addition, the woman fails to lactate and may have hypoglycemia.91,92,94 Investigation should include levels of ACTH, cortisol, prolactin, and free thyroxine. The ACTH stimulation test would be normal, as the adrenal cortex would not be atrophied. Thyroxine levels may prove normal initially, as the hormone has a half-life of seven days. Prolactin levels are usually low, although they are generally 5-10 fold elevated in the puerperium,. Treatment with saline and stress doses of corticosteroids should be instituted immediately after drawing the blood tests. Additional pituitary testing with subsequent therapy should be delayed until recovery. Diabetes insipidus may also occur secondary to vascular occlusion with atrophy and scarring of the neurohypophysis.95

When milder forms of infarction occur, the diagnosis of Sheehan’s syndrome may be delayed for months or years.95 These women generally have a history of amenorrhea, decreased libido, failure to lactate, breast atrophy, loss of pubic and axillary hair, fatigue, and symptoms of secondary adrenal insufficiency with nausea, vomiting, diarrhea, and abdominal pain.(Table 3)95 Some women experience only partial hypopituitarism, and may have normal menses and fertility.94 Although the women may have episodes of transient polydipsia and polyuria, many demonstrate impaired urinary concentrating ability and deficient vasopressin secretion.96 CT or MRI scans generally reveal partial or completely empty sellae.97

Lymphocytic hypophysitis is thought to be autoimmune in nature, and is manifested by a massive infiltration and destruction of the parenchyma of the pituitary and infundibulum by lymphocytes and plasma cells.98 It generally occurs during pregnancy or the postpartum period, perhaps related to the enolase autoantigen shared by both the pituitary and placenta.99 It is associated with symptoms of hypopituitarism or an enlarging mass lesion with headaches and visual field defects, and is suspected based on its timing and lack of association with an obstetric hemorrhage or prior history of menstrual difficulties or infertility. It is generally associated with mild hyperprolactinemia (<150 ng/ml) and diabetes insipidus. Differentiation from a pituitary neoplasm cannot be made based on CT or MRI scans which reveal a sellar mass with possible extrasellar extension, but only on biopsy results.100,101 Serum antibodies to human pituitary membrane antigens are specific, but not sensitive, for diagnosis.102 Treatment is generally conservative and involves identification and correction of any pituitary deficits, particularly of ACTH secretion, which is particularly common in this condition.103 There are no data to indicate that high dose corticosteroids are of benefit in treating the destructive process. Surgery to debulk but not remove the gland is indicated in the presence of uncontrolled headaches, visual field defects, and progressive enlargement on scan. Spontaneous regression and resumption of partial or normal pituitary function may occur, although most patients progress to chronic panhypopituitarism.103-105 Other autoimmune disorders may also be associated.

Hyperventilation in pregnancy leads to hypercapnea, renal bicarbonate wasting, and associated renal sodium loss. The osmostat, the setpoint for plasma osmolality at which arginine vasopressin (AVP) is secreted, is reduced approximately 5-10 mOsm/kg in pregnancy, dropping from 285 to 275 mOsm/kg. As a result, pregnant women experience thirst and release AVP at lower levels of plasma osmolality than do nonpregnant women.106 This reset osmostat and altered thirst threshold is possibly due to high levels of human chorionic gonadotropin (hCG).106 The placenta produces an amino-terminal peptidase, vasopressinase, an enzyme that rapidly inactivates AVP and oxytocin. Vasopressinase levels increase 1000-fold between the 4th and 38th weeks of gestation.107 AVP consequently has a four- to sixfold increased metabolic clearance rate during gestation.108,109

The lower osmostat and increased clearance of AVP by vasopressinase in pregnancy alter the nomograms of plasma osmolality and AVP used in the nonpregnant patient. Serum sodium levels may also be lower than those normally expected in patients with diabetes insipidus.109 Standard water deprivation tests which require 5% weight loss should be avoided during pregnancy as they may cause uterine irritability and alter placental perfusion. Instead, dDAVP is used to assess urinary concentrating ability over 11 hours, with a value greater than 700 mosm/kg considered normal.110 Urinary concentrating ability in the pregnant patient should be determined in the seated position, as the lateral recumbent position inhibits maximal urinary concentration.106,109 Delivery of the placenta generally results in a return to normal AVP metabolism in 2 to 3 weeks.

Plasma oxytocin levels increase progressively during pregnancy, with a dramatic increase at term.111,112 Oxytocin levels rise further during labor and peak in the second stage. Uterine sensitivity to oxytocin increases with a rise in oxytocin receptors in the myometrium. Hypophysectomy does not alter onset of labor, indicating that oxytocin provides only a facilitatory role.113 Pulsatile release of oxytocin does not correlate with uterine contractions. Oxytocin levels rise rapidly during suckling.114

Three types of diabetes insipidus may occur in pregnancy; central, nephrogenic, or transient vasopressin-resistant. Each is manifest with polydipsia, polyuria, and dehydration.

Central diabetes insipidus may occur spontaneously in pregnancy with an enlarging pituitary adenoma, with lymphocytic hypophysitis, or with the development of other conditions such as histiocytosis X. Diabetes insipidus usually worsens during gestation,109 likely due to the increased clearance of AVP by the vasopressinase. Patients with asymptomatic DI may develop symptoms during pregnancy with the lower osmostat for vasopressin release, elevation in vasopressinase levels, and increased AVP clearance.115-117 Patients with mild disease usually treated with chlorpropamide should discontinue this agent, as it readily crosses the placenta and causes hypoglycemia in the fetus. The AVP analog desmopressin (dDAVP) is resistant to vasopressinase, and provides satisfactory treatment during gestation, although a higher dose may be required.109 During monitoring of the clinical response, clinicians should remember that normal basal plasma osmolality and sodium concentration are 5 mEq/L lower during pregnancy.118 No adverse events have been described in the offspring of pregnancies in which dDAVP was used throughout gestation.119,120 DDAVP transfers minimally into breast milk109 and is poorly absorbed from the gastrointestinal tract, so its use will not adversely affect an infant’s water metabolism.

Transient AVP-resistant forms of DI secondary to placental production of vasopressinase may occur spontaneously in one pregnancy, but not in a subsequent one.118 Some of these patients may respond to dDAVP therapy. The symptoms resolve within several weeks of delivery.109,118,121

Acute fatty liver of pregnancy and other disturbances of hepatic function such as hepatitis may be associated with late onset transient DI of pregnancy in some patients.122,123 It is presumed the hepatic dysfunction is associated with reduced degradation of vasopressinase, further increasing vasopressinase levels and the clearance of AVP. The polyuria may develop either prior to delivery or postpartum. Complete resolution of the hepatic abnormalities and DI occurs by the 4th week postpartum.

DI that develops postpartum may be a result of Sheehan’s syndrome, particularly in the setting of an obstetric hemorrhage.(see above) Transient DI of unknown etiology has been described postpartum, lasting only days to weeks.124

Congenital nephrogenic DI is a rare X-linked disorder caused by a mutation in the vasopressin V2 receptor gene, and predominantly affects males. Female carriers of this disease may have significant polyuria during pregnancy. Treatment is with thiazide diuretics,109 which should be used with caution in pregnant women.

In patients with idiopathic DI, oxytocin levels are normal and labor may begin spontaneously and proceed normally.125 Patients with DI secondary to trauma, infiltrative disease, or a neoplasm may have adversely affected oxytocinergic pathways, resulting in poor progression of labor and uterine atony.