Myxedema Coma Nested Inside Sheehan Syndrome: A Diagnosis Not to Be Missed

Abstract

Myxedema crisis is a life-threatening manifestation of severe, decompensated hypothyroidism. It often presents insidiously with altered mental status, hypothermia, hypotension, bradycardia, and hypoglycemia. Sheehan syndrome is a rare but important cause of hypopituitarism, resulting from ischemic necrosis of the anterior pituitary due to severe postpartum hemorrhage. The condition may remain undiagnosed for years, with subtle symptoms gradually progressing to full-blown endocrine crises during physiological stress. We report the case of a 48-year-old woman who presented with sudden unconsciousness, hypotension, bradycardia, hypoglycemia, and hyponatremia. Her obstetric history revealed massive postpartum hemorrhage 15 years back, followed by failure of lactation and secondary amenorrhea. Physical examination revealed madarosis. Laboratory investigations confirmed central hypothyroidism and secondary adrenal insufficiency. Magnetic resonance imaging (MRI) of brain showed an empty sella turcica, supporting the diagnosis of Sheehan syndrome. She was managed with intravenous hydrocortisone and replacement dose of levothyroxine. Considering the clinical deterioration after initial improvement, levothyroxine 500 μg loading dose was given, suspecting myxedema coma, which lead to gradual improvement of sensorium and hemodynamic status. This case highlights the importance of considering myxedema coma in women with Sheehan syndrome, especially in the setting of an unexplained altered sensorium even after hydrocortisone supplementation.

Introduction

Sheehan syndrome is a condition characterized by hypopituitarism due to postpartum ischemic necrosis of the pituitary gland. It was first described in 1937 by Sheehan [1]. Patients with Sheehan syndrome have varying degrees of anterior pituitary hormone deficiency [2]. It is still a significant cause of maternal morbidity and mortality in developing countries despite the advanced obstetrical care. The diagnosis of this rare syndrome is not always apparent immediately after childbirth and it may take years to diagnose. When exposed to a stressful situation, the symptoms may be precipitated due to deficiency of cortisol. The first and most common symptom of Sheehan syndrome is the failure of lactation after childbirth. Anemia, hypotension, hypogonadotropic hypogonadism, central hypothyroidism are other common findings [3].

Central hypothyroidism is characterized by inappropriately low thyroid-stimulating hormone (TSH) in a background of low thyroid hormone levels which can result in dysfunction of heart rate, body temperature, and metabolism. Myxedema coma is a life-threatening emergency resulting from extremely low levels of thyroid hormones. Clinical signs and symptoms include hypothermia, coma, hypotension, bradycardia, hypercapnia, and hypoxemia. Early identification and initiation of treatment is the key for decreased mortality and morbidity. Sheehan syndrome presenting as myxedema coma, has been less reported in literature [4].

Case Presentation

A 48-year-old woman was admitted to the hospital with altered sensorium and history of recurrent vomiting. On initial assessment low blood pressure (80/50 mmHg) and hypoglycemia (capillary blood glucose 38 mg/dL or 2.11 mmol/L) were identified, Glasgow coma scale was 9/15 (eye opening to pain, withdraws from pain, inappropriate words). On detailed enquiry, her relatives informed that she was experiencing some fatigue and dizziness for the past 2 weeks, for which she did not seek any medical help. The patient experienced 2 similar episodes, one 2 years ago and another 5 years ago; one of the episodes required hospitalization but the details were not available. The patient had no other comorbidities. She had no history of trauma, surgery, or radiation treatment. The history of last childbirth was 15 years ago, following which she experienced massive vaginal bleeding and required 2 units of blood transfusion. After delivery she failed to lactate and remained amenorrhoeic and was not able to conceive.

On physical examination, her pulse rate was 54 beats/minute, respiratory rate 16 breaths/minute, temperature measured by oral thermometer was 93 °F (33.9 °C). Further examination revealed dry, coarse skin, wrinkling around mouth and eyes, madarosis, thin sparse hair, and generalized paleness without mucosal discoloration. Axillary and pubic hair was noted to be remarkedly decreased. A gynecological examination showed vaginal dryness and atrophy. The neurological examination showed decreased deep tendon reflex. Examination of cardiovascular and gastrointestinal system was unremarkable. No clinical sign of pericardial effusion has been identified.

Diagnostic Assessment

Initial laboratory investigations (Table 1) showed hyponatremia 121 mEq/L (121 mmol/L) [reference range, 135-145 mmol/L] with hypokalemia 3.3 mEq/L (3.3 mmol/L) [reference range, 3.5-5.1 mmol/L]. Arterial blood gas showed hypoxemia and hypercarbia suggestive of respiratory acidosis (Table 1). Complete blood count and creatinine were unremarkable. Electrocardiography (ECG) was suggestive of bradycardia and chest x-ray was unremarkable. Thyroid function status showed low free thyroxine (T4) 0.04 ng/dL (0.51 pmol/L) (reference range, 0.69-1.78 ng/dL [8.88-22.9 pmol/L]) with inappropriately normal TSH 2.24 µIU/mL (2.24 mIU/L) (reference range, 0.35-5.1 µIU/mL [0.35-5.1 mIU/L]). In addition, low cortisol 2.26 µg/dL (71.73 nmol/L) (reference range, 6.2-19.4 µg/dL [171-535 nmol/L]) with inappropriately normal adrenocorticotrophic hormone (ACTH) of 15 pg/mL (3.30 pmol/L) (reference range: 10-60 pg/mL [2.2-13.21 pmol/L]) was also found. All these point toward hypopituitarism. MRI of the hypothalamic pituitary region (Fig. 1A and 1B) showed empty sella. Based on history, clinical findings, and laboratory investigations, a diagnosis of Sheehan syndrome with adrenal insufficiency and central hypothyroidism was made.

Table 1.

Laboratory investigations

Parameters	Value	Unit	Reference range
Hemoglobin	11.2 112	gm/dL g/L	12.5-17 gm/dL 125-170 g/L
TLC	5600 5.6 × 10⁹	/mm3 /L	4000-11000/mm3 4.0-11.0 × 10⁹/L
DC	N50L38	%	N 40-70% L 20-40%
Platelet	1.7 170 × 10⁹	Lakh/mm3 /L	1.5-4 Lakh/mm3 150-400/L
Serum sodium	121 121	mEq/L mmol/L	135-145 mEq/L 135-145 mmol/L
Serum potassium	3.3 3.3	mEq/L mmol/L	3.5-5.1 mEq/L 3.5-5.1 mmol/L
Creatinine	0.9	mg/dL
eGFR	79	mL/min/1.73 m2
ABG	pH 7.27 pO2 54 mmHg pCO2 52 mmHg HCO3 27.2 mmol/L
TSH	2.24 2.24	μIU/mL mIU/L	Adult female: 0.35-5.1 μIU/mL 0.35-5.1 mIU/L
Free T4	0.04 0.51	ng/dL pmol/L	0.69-1.78 (ng/dL) 8.88-22.9 (pmol/L)
Serum cortisol (8AM)	2.26 71.73	μg/dL nmol/L	6.2-19.4 (μg/dL) 171-535 (nmol/L)
LH/FSH	4.4/17.7	mIU/mL

Abbreviations: ABG, arterial blood gas; DC, differential count; eGFR, estimated glomerular filtration rate; FSH, follicle-stimulating hormone; LH, luteinizing hormone; T4, thyroxine; TLC, total leukocyte count; TSH, thyroid-stimulating hormone.

Figure 1.

(A and B) MRI of the hypothalamic pituitary region (sagittal section) showing empty sella.

Treatment

Immediate management with 100 mg intravenous hydrocortisone at the emergency department followed by hydrocortisone 50 mg intravenously every 6 hours was started. Levothyroxine 75 µg/day was added the next day. Blood samples were drawn prior to hydrocortisone injection.

Outcome and Follow-Up

Sensorium and blood pressure improved after the initial hydrocortisone injection. On day 2, the patient was alert, conscious and cooperative, and her blood pressure was 114/84 mmHg. Hypoglycemia and hyponatremia were also corrected. Serum sodium was 131 mEq/L (131 mmol/L) on day 2. On day 3, the patient's sensorium deteriorated again. Neurological status on the Glasgow coma scale was 9 out of 15 (eye response to pain, inappropriate words, withdrawal from pain). Blood pressure was 90/60 mmHg. Repeat arterial blood gas showed persistence of respiratory acidosis. Serum sodium decreased to 128 mEq/L (128 mmol/L). Capillary blood glucose was 136 mg/dL (7.55 mmol/L). The altered sensorium even after correcting sodium and cortisol levels, pointed toward impending myxedema coma. Score for myxedema coma was 100 (presence of hypothermia, bradycardia, altered sensorium, hyponatremia, hypoxemia, hypercarbia, and hypotension). Suspecting myxedema coma, a 500-µg loading dose of levothyroxine was given via nasogastric tube followed by further maintenance dose of 75 µg daily. From day 4, her sensorium began to improve again. The patient became completely alert and conscious day 5 onward. Hemodynamic parameters improved as well. Intravenous hydrocortisone was gradually tapered and shifted to oral hydrocortisone after the initial crisis was over. The patient stabilized clinically and biochemically. She was discharged on day 10 with maintenance hydrocortisone (15 mg/day) and levothyroxine (75 µg). At the time of discharge, Glasgow coma scale was 15/15 and she could walk independently, serum sodium was 133 mEq/L (133 mmol/L).

Discussion

This case illustrates the delayed presentation of Sheehan syndrome presenting as adrenal insufficiency and myxedema coma. In this case, the patient's sudden onset of unconsciousness, hypoglycemia, and hypotension are hallmarks of adrenal insufficiency. Her history of postpartum hemorrhage 15 years prior, followed by failure of lactation, amenorrhea, and infertility, aligns with classic indicators of Sheehan's syndrome. Delayed diagnosis of Sheehan syndrome is relatively common, as clinical features are often subtle [5]. Rabee et al reported average delay of 20 ± 8.3 years with a range of 2 to 36 years was reported in 124 patients with Sheehan syndrome [6]. In one study mean diagnostic delay was found to be 9 ± 9.7 years in 39 women [7]. Hyponatremia as an initial symptom of Sheehan syndrome has been noted in approximately 60% of reported cases [8]. Glucocorticoid deficit leads to inappropriate secretion of vasopressin. The hypersecretion of vasopressin can be due to reduction in cardiac output and blood pressure induced by the absence of cortisol [9]. But Sheehan syndrome presenting as myxedema coma is seldom found. Previously one case report has been published where a 36-year-old woman with Sheehan syndrome presented as myxedema coma with hematological abnormalities [10]. In another case report, a 35-year-old multiparous female individual presented with hyponatremia in a background of seizure. She had a definite history of secondary amenorrhea and lactational failure. Biochemical findings showed suppression of all pituitary hormones [11]. Fredrick et al documented a case of 35-year-old woman, with a medical history of Sheehan syndrome and transient diabetes insipidus, presenting as myxedema coma and adrenal crisis together [12]. Although no gross focal neurological deficit was present in this case, hypoglycemia was found at the initial presentation. Apart from thyroid and adrenal axis, luteinizing hormone/follicle-stimulating hormone, prolactin was also low. Kaur et al mentioned 2 cases in their literature, where one man and another woman with central hypothyroidism presented as myxedema coma. The woman was in her 30s and presented with bradykinesia and shock and was diagnosed with Sheehan syndrome [13]. About 95% of myxedema coma is due to primary hypothyroidism and 5% of cases contributed by pituitary causes (central cause). A number of factors have been found to precipitate myxedema coma: sepsis, hypoxia, hyponatremia, cerebrovascular accidents, acute febrile illness, and heart failure. Early suspicion and prompt initiation of intravenous glucocorticoid followed by a loading dose of levothyroxine helped in restoration of hemodynamic stability of the patient. This case highlights that in any female patient with history of postpartum pituitary dysfunction and unconscious state, diagnosis of myxedema coma should be considered in addition to secondary adrenal insufficiency.

Learning Points

• Failure of lactation and amenorrhea are the initial manifestations of Sheehan syndrome.

• Consider Sheehan syndrome in women presenting with secondary adrenal insufficiency and myxedema coma with history of postpartum hemorrhage, even long ago.

• Secondary hypothyroidism can present with myxedema coma.

• Prompt diagnosis and early hormone replacement with hydrocortisone followed by loading and maintenance dose of levothyroxine is lifesaving.

Contributors

All authors made individual contributions. P.S., P.S., and R.P. were involved in diagnosis and management of the patient. A.A. and A.D. were involved in manuscript drafting and review. All authors approved the final version.

Abbreviations

MRI

magnetic resonance imaging

TSH

thyrotropin (thyroid-stimulating hormone)

Funding

No public or commercial funding.

Disclosures

None declared.

Informed Patient Consent for Publication

Signed informed consent obtained directly from the patient.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.