The diagnosis of Sheehan’s syndrome is determined by the patient’s history and physical examination, and confirmed by laboratory tests. Hemorrhagic shock during pregnancy is a key leading point in diagnosis. Failure to lactate is often a common initial complaint in patients with Sheehan syndrome [
15]. Many of them also report amenorrhea after delivery [
16]. The diagnosis of Sheehan’s syndrome is not made until several years later in certain cases, when the features of hypopituitarism become apparent in a woman who had postpartum bleeding [
17]. A woman with Sheehan’s syndrome with undiagnosed hypopituitarism might be apparently asymptomatic until her body is exposed to stressful situations like surgery or infection many years after her delivery, and then she presents with adrenal crisis [
18]. Sheehan’s syndrome presents with varied symptoms depending on the specific anterior pituitary hormone deficiencies. Prolactin deficiency can cause lactation failure. Gonadotropin deficiency will often cause amenorrhea or genital hair loss. Corticotrophin deficiency can result in generalized fatigue, weakness, hypoglycemia, or dizziness. Growth hormone deficiency causes fatigue, decreased quality of life, and weight loss. Symptoms of central hypothyroidism are clinically similar to primary hypothyroidism, but patients with central hypothyroidism have low triiodothyronine and thyroxine levels, with normal or even inappropriately low thyroid-stimulating hormone levels. Diagnosis of panhypopituitarism is straightforward, but partial deficiencies are often difficult to determine [
19]. Sheehan's syndrome can be acute or chronic [
20]. Acute cases present with failure to lactate or amenorrhea. Our patient could not breastfeed following her pregnancy due to lactation failure, and became amenorrheic, indicating an acute presentation. In the previously mentioned study in France, the mean diagnostic delay was 2.52 ± 3 months for patients with agalactia and 8.3 ± 8 years for patients with amenorrhea [
9]. Moreover, our patient also developed signs and symptoms of chronic Sheehan’s syndrome, which include secondary adrenal insufficiency such as asthenia, anorexia, and weight loss progressing to dizziness, nausea, vomiting, and abdominal pain, for which she had repeatedly visited health care providers, but the diagnosis was missed. The French study found that the delay in diagnosis in patients presenting with hypothyroidism was 8.1 ± 8.5 years and in those presenting with acute adrenal insufficiency was 10.6 ± 9.4 years [
9]. In patients who present with acute disease progressing to chronic conditions, the diagnosis could have been made at several stages. In our patient, the first clue to her diagnosis was her lactational failure and amenorrhea, and the next clue was the manifestation of symptoms of adrenal insufficiency in subtle ways with fatigue and anorexia which progressed to dizziness, nausea, vomiting, and abdominal pain, all of which were missed as findings in making a diagnosis. This can be attributed to a lack of awareness, especially given that patients with panhypopituitarism present with varied nonspecific symptoms, coupled with a lack of a thorough history and physical examination required to diagnose a rare disease.
Laboratory tests can reveal many other anomalies, including hyponatremia. This is the most common electrolyte imbalance, occurring in 33–69% of cases [
21,
22]. There are several possible mechanisms by which hypopituitarism can result in hyponatremia. Hypothyroidism can cause decreased free-water clearance and subsequent hyponatremia. Glucocorticoid deficiency can also cause decreased free-water clearance, independent of vasopressin. Hypopituitarism itself can stimulate vasopressin secretion and can cause severe inappropriate secretion of antidiuretic hormone, which can also cause hyponatremia. The potassium level in these situations is normal, because adrenal production of aldosterone is not dependent on the pituitary. In this case the initial hypokalemia noted could be due to gastrointestinal loss following diarrhea and vomiting. The patient’s sodium level subsequently normalized with commencement of hormone replacement therapy, and potassium was corrected with intravenous potassium chloride (KCL) administration.
Anemia is well recognized as a feature of hypopituitarism. Gokalp
et al. recently reported hematological abnormalities in 65 patients with Sheehan’s syndrome, 80% of whom presented with anemia, compared with 25% of controls [
3]. Many hormonal deficiencies, including hypothyroidism, adrenal insufficiency, and gonadal hormonal deficiency, can explain normochromic anemia in hypopituitarism [
23]. Pancytopenia is rarely observed in patients affected with Sheehan’s syndrome, and a literature review reveals the rarity this disorder. Our patient had bicytopenia with mild normochromic normocytic anemia. The possibility of Sheehan’s syndrome was suspected because of her obstetric history, signs and symptoms of chronic adrenal insufficiency, hyponatremia, and baseline hormone levels. MRI study of the pituitary gland may reveal different features depending on the stage of the disease. While early scans are not usually helpful for diagnosis, they demonstrate a nonhemorrhagic enlargement of the pituitary gland, leading to its subsequent involution, and late scans typically show an empty sella. A secondary empty sella is considered a characteristic finding in the classical form of Sheehan’s syndrome [
24]. Treatment of young women with hypopituitarism usually includes replacement of hydrocortisone first and then replacement of thyroid-stimulating hormone and estrogen with or without progesterone, depending on whether the woman has a uterus. Hydrocortisone is replaced first because thyroxin therapy can exacerbate glucocorticoid deficiency and theoretically induce an adrenal crisis [
16,
25]. The standard dose of hydrocortisone is 20 mg/day for an adult (15 mg every morning and 5 mg every evening). Both thyroxin replacement and gonadotropin replacement are common, and doses are titrated to each individual. Replacement of growth hormone is necessary in children with hypopituitarism but is controversial in adults. Some people with severe growth hormone deficiency derive great benefit from replacement, but standard recommendations are not available [
26]. For our patient, we replaced relevant and available hormones considering her age, fertility desire, and affordability.