patients with growth hormone ( gh ) deficiency who have a history of abnormal birth injury such as breech delivery occasionally show an atrophic anterior lobe of the pituitary gland , the formation of an ectopic posterior lobe at the median eminence , and a thin or absent pituitary stalk on brain magnetic resonance imaging ( mri ) ( 1 ) .
gh insufficiency develops first , followed by insufficiencies of gonadotropins and thyroid stimulating hormone ( tsh ) during childhood , and finally adrenocorticotropic hormone ( acth ) insufficiency in later adulthood ( 2,3 ) .
successful pregnancy in hypopituitarism is rare , given its association with an increased risk of pregnancy complications , such as abortion , anemia , pregnancy - induced hypertension , placental abruption , premature birth , and postpartum hemorrhage , as reviewed by du et al .
gh replacement therapy ( ghrt ) is not officially licensed for use during pregnancy because of the lack of sufficient safety data .
pregnant patients receiving ghrt are often concerned about whether or not they should stop ghrt , and most physicians have reported making a decision on whether or not to continue ghrt in agreement with the patient 's wish ( 6 ) .
we herein describe the successful pregnancies and deliveries in a patient with evolving hypopituitarism due to pituitary stalk transection syndrome who partially continued gh , thyroid hormone , and glucocorticoid replacement therapy during pregnancy .
a 31-year - old japanese woman visited our hospital because of adrenal insufficiency after her first delivery .
she was born by breech delivery at 31 weeks ' gestation , weighing 1,040 g. at the age of 7 years , she presented with growth retardation and was diagnosed with gh deficiency using an insulin - induced hypoglycemia and arginine test .
she did not visit our hospital for 5 years from age 15 until age 20 but returned to the department of obstetrics and gynecology because of primary amenorrhea .
she succeeded in becoming pregnant after several inductions of ovulation and delivered a healthy male baby weighing 2,795 g , as described by fukuta et al .
she received ghrt again 10 months after the first delivery from her primary care doctor ( table 1 ) .
clinical course of hormonal data in a patient with evolving hypopituitarism at and after the first delivery .
she was referred to the department of endocrinology and metabolism at our hospital by her primary care doctor because her laboratory tests showed adrenocortical insufficiency at 31 years of age .
her free t4 was low despite levothyroxine replacement , and her adrenocortical function was diagnosed as mildly insufficient for the first time on the basis of her endocrinological data ( table 2 ) . a low dose of hydrocortisone ( 5 mg daily )
was added to levothyroxine ( 50 g daily ) and somatropin ( 0.45 mg daily ) .
her ghrt was reduced to two - thirds of the pregestational dose ( 0.3 mg daily ) at 8 weeks ' gestation and discontinued at 26 weeks ' gestation .
thyroxine was increased to 75 g daily after 8 weeks ' gestation and 100 g daily after 26 weeks ' gestation , so that the serum free t4 levels remained 0.7 - 1.1 ng / dl during pregnancy .
we carefully followed her with monthly measurements of the serum levels of gh , insulin - like growth factor ( igf)-1 , acth , cortisol , and thyroid hormone during her second pregnancy , as shown in figure .
her gh levels rose gradually after the second trimester , but the igf-1 levels were maintained until delivery .
she had remained normotensive , and neither proteinuria nor glycosuria was observed during her second pregnancy . under spontaneous labor , she delivered a male baby weighing 3,320 g at a gestation of 40 weeks and 1 day .
her serum gh and igf-1 levels fell rapidly three days after delivery , and so the ghrt was restarted .
the latest follow - up showed that her two children aged 5 and 2 were both mentally and physically healthy .
changes in the serum levels of igf-1 , gh , and cortisol , and in the plasma levels of acth during the second pregnancy and after delivery .
an intact gh - igf1 axis is not always essential for normal fertility , but it has been claimed that gh deficiency leads to difficulties in conception and subfertility ( 8) . the role of gh supplementation in the prevention of fertilization problems or early gestational complications in gh - deficient women ( 8 - 10 ) should to be clarified . the efficacy and safety of ghrt during pregnancy is also a matter of debate ( 9 - 12 ) . during normal pregnancy , the pulsatile release of pituitary gh is progressively suppressed and replaced by a continuous secretion of placental gh .
gh does not cross the placenta , and its effects on the fetus are probably indirect and mediated by maternal igf-1 production and actions on the substrate supply to the fetus ( 13 ) .
therefore , it is justifiable to continue ghrt in women with definite gh deficiency at least until sufficient production of placental gh is achieved ( 14 ) . in the present case
the proteinuria was observed at the late stage of third trimester in the first pregnancy but not in the second pregnancy , suggesting that proteinuria may not be an adverse effect of ghrt .
very recently , vila et al . ( 6 ) reported the pregnancy outcomes in a large group of patients ( 173 women in 15 countries ) with gh deficiency and hypopituitarism .
three different ghrt regimens were adapted : 1 ) ghrt stopped before or as soon as the pregnancy was confirmed , 2 ) ghrt partially continued and stopped at the end of the second trimester , and 3 ) ghrt continued throughout the pregnancy .
the different regimens did not seem to influence the percentages of live births ( 80.5% in women who continued ghrt and 80.4% in women who stopped ghrt completely ) .
they concluded that pregnancy outcomes and pregnancy complications , such as gestational diabetes , pre - eclampsia and pregnancy - associated hypertension , were not related to the ghrt patterns , method of conception , or number of additional pituitary hormone deficiencies ( 6 ) .
we reported the successful pregnancies and deliveries in a patient with evolving hypopituitarism due to pituitary stalk transection syndrome who partially continued gh , thyroid hormone , and glucocorticoid replacement therapy during pregnancy .
we hope this report encourages patients with hypopituitarism who wish to have a successful pregnancy and delivery , although the optimal management of hypopituitarism during pregnancy and delivery has not been determined yet .
the clinical course of the present case was presented at the 87th annual meeting of the japan endocrine society in april , 2014 .
 we herein report a 31-year - old japanese woman with evolving hypopituitarism due to pituitary stalk transection syndrome . she had a history of short stature treated with growth hormone ( gh ) in childhood and had hypothyroidism and primary amenorrhea at 20 years old . 
 levothyroxine replacement and recombinant follicle stimulating hormone - human chorionic gonadotropin ( fsh - hcg ) therapy for ovulation induction were started . 
 gh replacement therapy ( ghrt ) was resumed when she was 26 years old . 
 she developed mild adrenocortical insufficiency at 31 years old . 
 she succeeded in becoming pregnant and delivered twice . 
 ghrt was partially continued during pregnancy and stopped at the end of the second trimester without any complications . 
Introduction
Case Report
Discussion
The authors state that they have no Conflict of Interest (COI).
Disclosure