Amenorrhea (Sheehan Syndrome) Case File

Amenorrhea (Sheehan Syndrome) Case File

Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD

CASE 51

A 24-year-old G2P2 woman delivered vaginally 8 months previously. Her pregnancy was unremarkable and she states that she had no medical problems. Her delivery was complicated by postpartum hemorrhage requiring curettage of the uterus and a blood transfusion of four units of erythrocytes. She complains of amenorrhea since her delivery. She denies taking medications or having headaches or visual abnormalities. Her pregnancy test is negative. She was not able to breastfeed her baby.

» What is the most likely diagnosis?

» What is the likely mechanism for the condition?

» What are other complications that are likely with this condition?

ANSWER TO CASE 51:

Amenorrhea (Sheehan Syndrome)                                           

Summary: A 24-year-old G2P2 woman has had amenorrhea since a vaginal delivery complicated by postpartum hemorrhage and uterine curettage. She was not able to lactate.

• Most likely diagnosis: Sheehan syndrome (anterior pituitary necrosis).
• Mechanism: Pregnancy-associated enlargement of the anterior pituitary gland and hypotension leading to hemorrhage into the anterior pituitary gland.
• Other complications that are likely with this condition: Anterior pituitary insufficiency, such as hypothyroidism or adrenocortical insufficiency.

ANALYSIS

Objectives

1. Be able to differentiate the clinical presentation of Sheehan syndrome from intrauterine adhesions (IUAs; Asherman syndrome).
2. Understand the mechanism of Sheehan syndrome.
3. Know the other tropic hormones that may be affected by anterior pituitary necrosis.

Considerations

This patient developed amenorrhea from the time of her vaginal delivery that was complicated by postpartum hemorrhage. This patient has secondary amenorrhea (see also Case 49). The initial evaluation should be a pregnancy test (which is negative). The patient also underwent a uterine curettage in the treatment of the postpartum bleeding. In this setting, there are two explanations: (1) Sheehan syndrome and (2) intrauterine adhesions (Asherman syndrome). Sheehan syndrome is caused by hypotension in the postpartum period, leading to hemorrhagic necrosis of the anterior pituitary gland. Asherman syndrome is caused by the uterine curettage, which damages the decidua basalis layer, rendering the endometrium unresponsive. The key to differentiating between Sheehan syndrome and intrauterine adhesions is to assess for whether or not the anterior pituitary is functioning, and whether the outflow tract (uterus) is responsive to hormonal therapy. For instance, since this patient’s history was “unable to breastfeed after delivery,” it would suggest that the anterior pituitary was not functioning (lack of prolactin). Had the patient been able to breastfeed, the most likely diagnosis would have been intrauterine synechiae. This patient was given a combination oral contraceptive agent, and if the endometrium were responsive to the hormonal therapy, then proliferation of the endometrium should occur followed by stabilization of the endometrium with the progestin component, and then finally bleeding when the placebo pills are taken (days 21– 28). Other evidences of anterior pituitary dysfunction may include low thyroid hormones, gonadotropin (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]), or cortisol levels. A definitive diagnosis of IUA can be made with saline infusion sonohysterogram or hysterosalpingogram.

APPROACH TO:

Postpartum Amenorrhea                                             

DEFINITIONS

AMENORRHEA: No menses for 6 months.

SHEEHAN SYNDROME: Anterior pituitary hemorrhagic necrosis caused by hypertrophy of the prolactin-secreting cells in conjunction with a hypotensive episode, usually in the setting of postpartum hemorrhage. The bleeding in the anterior pituitary induces pressure necrosis.

INTRAUTERINE ADHESIONS (ASHERMAN SYNDROME): Scar tissue that forms in the endometrium, leading to amenorrhea caused by unresponsiveness of the endometrial tissue.

POSTPARTUM HEMORRHAGE: Classically defined as bleeding > 500 mL for a vaginal delivery and > 1000 mL for a cesarean delivery. From a more pathophysiologic standpoint, it is the amount of bleeding that results in, or threatens to result in, hemodynamic instability if left unabated.

CLINICAL APPROACH

Amenorrhea can ensue after a term delivery for 2 to 3 months; breast feeding may inhibit the hypothalamic function, and lead to a greater duration of amenorrhea. However, in a nonlactating woman, when no menses resumes by 12 weeks after delivery, then pathology must be suspected. Overall, the most common cause of amenorrhea in the reproductive years is pregnancy. Therefore, a pregnancy test is the appropriate initial test. If the patient does not have a history of postpartum hemorrhage, evaluation of hypothalamic causes, such as hypothyroidism or hyperprolactinemia, is often fruitful. If the patient is somewhat obese, or has a history of irregular cycles, then polycystic ovarian syndrome (PCOS) would be entertained. Findings consistent with PCOS include a positive progestin withdrawal bleed (vaginal bleeding after the ingestion of a progestin, such as medroxyprogesterone acetate or Provera). Polycystic ovarian syndrome is characterized by estrogen excess without progesterone, obesity, hirsutism, and glucose intolerance. Elevated luteinizing hormone to follicle-stimulating hormone ratios are often seen (eg, LH:FSH is of 2:1). Polycystic ovarian syndrome should be suspected in patients with obesity, hirsutism, and oligomenorrhea. When women are hypoestrogenic, then two broad categories of causes are common: hypothalamic/ pituitary diseases or ovarian failure. The FSH level can distinguish between these two causes, with an elevated FSH indicative of ovarian failure.

The patient in this case had amenorrhea after a vaginal delivery and postpartum hemorrhage, making Sheehan syndrome or intrauterine adhesions the two most likely causes. Distinguishing between these two entities involves assessing whether the patient has normal or abnormal anterior pituitary function, or some evidence of unresponsiveness of the outflow tract to hormonal treatment (Table 51– 1). The treatment of Sheehan syndrome consists of replacement of hormones, such as thyroxine, cortisol, and mineralocorticoid, and estrogen and progestin therapy. Intrauterine adhesions are treated by hysteroscopic resection of the scar tissue.

CASE CORRELATION See also Case 49 (Intrauterine Adhesions) and Case 50 (Hypothalamic Dysfunction Due to Galactorrhea) as two other causes of secondary amenorrhea. Pituitary causes are the least common. See also Case 6 (Postpartum Hemorrhage).

COMPREHENSION QUESTIONS

51.1 A 19-year-old G1Ab1 woman underwent a uterine curettage after a miscarriage. She has had no menses since then and is not pregnant. The physician is suspecting intrauterine adhesions. Which of the following is a feature of intrauterine synechiae (Asherman syndrome)?

A. Usually occurs after uterine curettage

B. Associated with low gonadotropin levels

C. Associated with a monophasic basal body temperature chart

D. Associated with low cortisol levels

51.2 A 24-year-old G1P1 woman is seen in the office with secondary amenorrhea after her delivery. She is given a tentative diagnosis of pituitary necrosis (Sheehan syndrome). Which of the following is consistent with her presumed diagnosis?

A. Usually associated with hypertensive crisis at or soon after a delivery

B. Caused by an ischemic necrosis of the posterior pituitary gland

C. Associated with decreased prolactin levels

D. Often associated with elevated thyroid-stimulating hormone (TSH) levels

51.3 A 32-year-old G2P1Ab1 woman presents to the gynecologist with 6 months of amenorrhea. Which of the following is the best description of the mechanism of intrauterine synechiae (Asherman syndrome)?

A. Trophoblastic hyperplasia

B. Pituitary engorgement

C. Myometrial scarring

D. Decidual hypertrophy

E. Endometrial disruption

51.4 A 25-year-old woman presents with a 6-month history of amenorrhea. Her pregnancy test is negative. She is evaluated for other causes of secondary amenorrhea, and is given a diagnosis of PCOS. Which of the following is consistent with this disorder?

A. Estrogen deficiency and vaginal atrophy

B. Osteoporosis

C. Endometrial hyperplasia

D. Hypoglycemia

E. A history of regular menses each month prior to 6 months

ANSWERS

51.1 A. Intrauterine adhesions are associated with a biphasic basal temperature chart that reflects normal pituitary function and normal ovulation. This indicates the presence of progesterone, which elevates the temperature. Intrauterine adhesions usually occur after curettage of the uterus. It is with Sheehan syndrome, and not with Asherman syndrome, that due to anterior pituitary hemorrhagic necrosis, the patient is unable to breastfeed after delivery, has a monophasic basal body temperature chart, and has low cortisol levels. The necrotic anterior pituitary is unable to secrete prolactin, FSH/ LH, ACTH, TSH, or growth hormone, and patients must take hormone replacements to restore function of the organs and systems these hormones acted upon.

51.2 C. Sheehan syndrome involves the anterior pituitary undergoing hemorrhagic necrosis after a hypotensive episode, usually in the setting of postpartum hemorrhage. The anterior pituitary is, therefore, unable to secrete prolactin among a few other hormones. The posterior pituitary is not involved because it has a direct arterial supply. Hypothyroidism is a result of Sheehan syndrome due to the low or absent TSH secretion from the anterior pituitary. A patient may have an associated hypotensive episode, and not a hypertensive one, in their peripartum period caused by the postpartum hemorrhage.

51.3 E. In Asherman syndrome, large patches of endometrium are defective because of intrauterine adhesions. The endometrium is unresponsive, so estrogen exposure will have no effect on the lining of the uterus, and therefore, cannot pose a risk for endometrial hyperplasia. Endometrial, and not myometrial, scarring is involved. Pituitary engorgement occurs during pregnancy due to the hypertrophy and hyperplasia of lactotrophs. There is no associated increase in vascular supply, so when postpartum hemorrhage occurs, the anterior pituitary is particularly vulnerable to ischemia. Trophoblastic hyperplasia originates from placental tissues. It does not directly induce intrauterine synechiae; however, if the patient undergoes a dilation and curettage for management of the trophoblastic disease, Asherman syndrome may develop.

51.4 C. PCOS is a condition characterized by chronic anovulation, hyperandrogenism where other causes have been eliminated, and possible evidence of small ovarian cysts on ultrasound. It is associated with unopposed estrogen and estrogen excess. This setting increases the patient’s risk of endometrial hyperplasia or endometrial cancer. Osteoporosis is a risk in hypoestrogenic states, and this patient has estrogen excess, so osteoporosis is not a concern; in fact, bone mineral density is usually quite good. Vaginal atrophy is associated with estrogen deficiency, not excess. Glucose intolerance, diabetes mellitus, and a history of oligomenorrhea since menarche are consistent with the diagnosis of PCOS.

    CLINICAL PEARLS    

» The two most common causes of secondary amenorrhea after postpartum hemorrhage are Sheehan syndrome and intrauterine adhesions. » A pregnancy test should be the first test in evaluating a woman with secondary amenorrhea. » Normal function of the anterior pituitary points toward intrauterine adhesions. » Hypothyroidism or a monophasic basal body temperature chart suggests Sheehan syndrome. » The treatment of Sheehan syndrome consists of replacement of the hormones governed by the anterior pituitary gland. » The most common cause of ovulatory dysfunction in a reproductiveaged woman is PCOS, which is characterized by obesity, anovulation, hirsutism, glucose intolerance, and estrogen excess.

REFERENCES

Alexander CJ, Mathur R, Laufer LR, Azziz R. Amenorrhea, oligomenorrhea, and hyper-androgenic disorders. In: H acker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 5th ed. Philadelphia, PA: Saunders; 2010:355-367. 

Lobo RA. Primary and secondary amenorrhea and precocious puberty. In: Katz VL, Lentz GM, Lobo RA, Gershenson DM, eds. Comprehensive Gynecology. 6th ed. St. Louis, MO: Mosby-Year Book; 2012:933-961.

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