Amanda H. Ritter
History of present illness
A 38-year-old gravida 1, para 1 woman presented 3 months postpartum with worsening fatigue, lethargy, and depression.
She had a term spontaneous vaginal delivery of an 8-lb boy, but her delivery was complicated by a retained placenta and postpartum hemorrhage of approximately 2000 cc. She required a manual placental extraction and uterine curettage, and was transfused four units of packed red blood cells postpartum.
Afterwards, the patient had an otherwise uneventful course but was unable to breast-feed her infant due to a failure to lactate.
She still has not had return of menses. The patient initially attributed her fatigue and lethargy to being a new mother.
However, these symptoms have progressively worsened. She also reports cold intolerance, inability to lose weight, and decreased libido.
She denies any other medical problems and has had no surgeries. She uses condoms for birth control. She takes no medications.
Physical examination
General appearance: Obese, white woman in no acute distress
Vital signs:
Temperature: 37.0°C Pulse: 54 beats/min
Blood pressure: 100/70 mmHg Respiratory rate: 12 breaths/min Oxygen saturation: 99% on room air
HEENT: Mild alopecia present; unremarkable otherwise Neck: Supple, no thyromegaly
Cardiovascular: Bradycardic rate; regular rhythm without murmurs, rubs, or gallops
Lungs: Clear to auscultation bilaterally
Breast: Normal appearing breasts bilaterally, no masses palpated, no nipple discharge expressed
Abdomen: Soft, obese, nondistended, active bowel sounds present. No tenderness to palpation in upper or lower quadrants bilaterally
Pelvic: Normal appearing external genitalia. Vaginal mucosa within normal limits, scant discharge. Parous cervix without lesions. Bimanual examination with small, anteverted, mobile, nontender uterus. No cervical motion tenderness. No adnexal masses or tenderness to palpation bilaterally
Extremities: Patches of erythematous, scaly skin on hands and anterior lower extremities
Neurologic: Delayed 2+ deep tendon reflexes, bilaterally;
nonfocal otherwise Initial laboratory studies:
Urine pregnancy test: Negative Hb: 11.5 g/dL
MCV: 83 fL
How would you further evaluate this patient?
This patient presents with amenorrhea, absence of lactation, fatigue, cold intolerance, and decreased libido. From her workup thus far, subsequent pregnancy and pelvic anatomic abnormalities have been excluded as a cause for her amenor- rhea. Additionally, her remaining symptoms and clinicalfind- ings are suggestive of possible depression, hypothyroidism, or malfunctioning of the hypothalamic–pituitary–ovarian axis.
A thyroid-stimulating hormone (TSH) level should be ordered to evaluate thyroid function as the next most likely cause of her symptoms. This patient’s TSH was 0.06 àIU/mL (0.35–5.5 àIU/mL). Her free thyroxine (T4) was 0.4 ng/dL (0.8–1.8 ng/dL). The low TSH and free T4 indicate a problem with the pituitary itself. At this time, further investigation of the hypothalamic–pituitary–ovarian axis is necessary with testing of cortisol, adrenocorticotropic hormone (ACTH), follicle- stimulating hormone (FSH), luteinzing hormone (LH), and prolactin. All of these values were low: cortisol 5μg/dL (5–23μg/dL), ACTH 10 pg/mL (9–52 pg/mL), FSH less than 0.3 mIU/mL, LH less than 0.1 mIU/mL, and prolactin 1.5 ng/mL (2–39 ng/mL). This patient shows evidence of panhypopituitarism, so imaging of the pituitary itself was ordered to further delineate a cause for this patient’s symp- toms. MRI of the brain revealed an empty sella with minimal pituitary tissue.
How would you manage this patient?
This patient has Sheehan syndrome. She presents with the typical history of postpartum hemorrhage, failure to lactate, and amenorrhea. She also displays symptoms of other pituitary deficiencies, including hypothyroidism. Her laboratory find- ings are significant for pan-hypopituitarism, and her imaging shows an empty sella turcica. Once the diagnosis was made, treatment was initiated with both steroids and levothyroxine under the guidance of an endocrinologist. Her symptoms
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
gradually begin to improve after initiation of hormone replace- ment therapy, and she is followed at regular intervals by both her gynecologist and endocrinologist.
Sheehan syndrome
Sheehan syndrome is a process that was first described by Harold L. Sheehan in the 1930s. Sheehan syndrome involves persistent hypopituitarism after pituitary ischemia caused by obstetrical blood loss and hypotension or shock. This syn- drome has become much rarer because of advances in the prevention and management of postpartum hemorrhage and the availability of blood products for transfusion. However, cases of Sheehan syndrome still happen, most frequently in developing countries with limited obstetrical resources or in areas where home births are still common [1].
Sheehan syndrome involves a wide range of clinical pre- sentations, ranging from immediate postpartum circulatory failure to mild symptoms manifesting many years after the sentinel event [2]. The average time between the inciting inci- dent and clinical manifestations varies from 1 to 40 years, and the timing of onset of presenting symptoms does not often correlate with the severity of symptoms [3]. The speed and onset of symptoms is determined by the extent of pituitary damage. Because the pituitary gland has significant reserve capacity, more than 75% of the gland must be destroyed before symptoms become evident [2]. In less severe cases of Sheehan syndrome, the absence of lactation after pregnancy due to low levels of prolactin is often the first evidence of postpartum pituitary necrosis. Affected women typically have failure of return of menses and scant regrowth of shaved pubic hair, both as a result of gonadotropin failure. Secondary hypothy- roidism, adrenal insufficiency, and growth hormone defi- ciency, manifested as low levels of TSH, free T4, cortisol, ACTH, and growth hormone often appear later [1,2]. Growth hormone deficiency has been found in all reported cases of Sheehan syndrome, whereas other hormones typically thought to be routinely involved, like TSH and prolactin, are actually variably present [4]. When Sheehan syndrome presents acutely, women may be confused, stuporous, or comatose.
These findings are all indications of severe hyponatremia, which can be another manifestation of Sheehan syndrome. In these cases, immediate cortisol and thyroxine replacement should be administered to enable the correction of the hyponatremia [2].
While radiologic imaging is not necessary for the diagnosis of Sheehan syndrome, evidence of partial or complete pituitary necrosis, or empty sella, on imaging further supports the diagnosis [1]. An empty sella may be visualized on MRI or CT (arrow,Fig. 65.1) [2]. Pituitary MRI is the most sensitive imaging for detecting Sheehan syndrome [3]. However, an empty sella is not specific for Sheehan syndrome. According to Sert and colleagues, an empty sella is visualized in approxi- mately 28.5% of MRI images and 20% of high-resolution CT images in women with Sheehan syndrome [2]. Given that an
empty sella is not diagnostic of Sheehan syndrome, other diagnoses presenting with this radiograph finding must also be ruled out, including postpartum necrosis of a pituitary adenoma and lymphocytic hypophysitis [3].
The management of Sheehan syndrome should begin with the replacement of the target hormones that have been found to be deficient. Adrenal function should be corrected first as adrenal insufficiency can be life-threatening [1]. The minimum glucocorticoid dose required to correct clinical symptoms should be administered and must be tailored to each individual case [3]. The administration of thyroid hormone replacement alone in a patient with unrecognized adrenal insufficiency can be extremely dangerous, as thyroid hormone replacement can increase the metabolic clearance of cortisol and exacerbate an adrenal crisis [1]. Once adrenal replacement is adequate, thyroid hormone replacement should be initiated and titrated to maintenance levels based on periodic serum TSH testing and clinical symptoms.
Premenopausal women with gonadotropin deficiency should be administered estrogen and progesterone. If a woman with Sheehan syndrome desires to become pregnant, ovulation induction may be necessary. Growth hormone replacement improves waist circumference, lipid profiles, visceral fat, and importantly, quality of life [3].
Key teaching points
The classic presentation of Sheehan syndrome involves a history of significant postpartum hemorrhage requiring blood transfusions or volume repletion followed by failure
Fig. 65.1 Empty sella (arrow) on MRI. Image from: Empty sella syndrome.
http://en.wikipedia.org/wiki/Empty_sella(Accessed November 21, 2013).
Case 65: A 38-year-old woman with worsening postpartum fatigue
of lactation and amenorrhea or other evidence of anterior pituitary malfunction.
The differential diagnosis of Sheehan syndrome includes pregnancy, depression, hypothyroidism, pituitary adenoma, and lymphocytic hypophysitis.
Radiographic imaging may display an empty sella, but this is not diagnostic of Sheehan syndrome. Pituitary MRI is the most sensitive imaging modality for Sheehan syndrome.
The onset and severity of symptoms can be extremely variable. Symptoms may be acute and so extreme as to cause hemodynamic instability and altered mentation.
Conversely, hypopituitarism may gradually begin as long as 40 years postpartum.
Treatment involves stabilization of the patient if symptoms are acute and severe. Deficient hormones need replacement. Steroids must be initiated prior to thyroid hormone replacement to prevent adrenal crisis.
References
1. Tessnow AH, Wilson JD. The changing face of Sheehan’s syndrome.Am J Med Sci2010;340:402–6.
2. Sert M, Tetiker T, Kirim S, Kocak M.
Clinical report of 28 patients with
Sheehan’s syndrome.Endocr J2003;
50:297–301.
3. Karaca Z, Tanriverdi F, Unluhizarci K, Kelestimur F. Pregnancy and pituitary disorders.Eur J Endocrinol2010;
162:453–75.
4. Dejager S, Gerber S, Foubert L, Turpin G. Sheehan’s syndrome:
Differential diagnosis in the acute phase.J Int Med1998;244:
261–6.