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Case Report

Sheehan's Syndrome Presenting with

Hyponatraemia: A Case Report

Prasanta Kumar Bhattacharya MBBS,MD,PhD,FICP,FACP,Aakash Roy MBBS,Md.Jamil MBBS,MD, Pranjal Phukan MBBS,MD,OM,Kalyan Sarma MBBS

Bhattacharya

Roy

Jamil

About the Authors

The authors practice at the North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, located in the north eastern city of Shillong in India. Prasanta K Bhattacharya is a professor and head of the Department of General Medicine.Aakash Roy is doing his post graduate course in General Medicine. Md Jamil is an assistant professor in general medicine. Pranjal Phukan is an associate professor of radiology. Kalyan Sarma is doing his post graduate course in radiology. Correspondence may be direded to: pkbdr78@gmail.com

Abstract

Sheehansyndrome (SS), or postpartum necrosis of the pituitary gland, is a rare complication of post partum haemorrhage usually presenting with failure of lactation and subsequent amenorrhoea. We report a case of a 30-year-old woman with history of secondary amenorrhea and lactational failure following childbirth complicated with severe post partum hemorrhage, who presented to us with anemia, hypotension, acute confusion, neuropsychiatric manifestations, abnormal posturing and severe hyponatraemia. Hormonal assays revealed low pituitary hormones, sub­ normal levels of cortisol and thyroid hormones, with magnetic resonance imaging of the brain suggestive ofSS. Hyponatraemia and late onset neuro-psychiatric manifestations are uncommon presentations of SS. Hence, there should be a high index of clinical suspicion for Sheehan's syndrome in women with secondary amenorrhea and lactational failure following childbirth, who present with late onset neuro-psychiatric manifestations and hyponatremia.

Key words: Sheehan's syndrome, hyponatremia, secondary amenorrhea, lactational failure, neuro-psychiatric manifestation

Resume

Le syndrome de Sheehan (SS), ou necrose postpartum de Ia glande pituitaire, est une complication rare consecutive a une hemorragie postpartum et qui se manifeste habituellement par !'absence de montee laiteuse et une amenorrhee subsequente. Nous decrivons le cas d'une femme de trente ans ayant des antecedents d'amenorrhee secondaire et de defaut de lactation a Ia suite d'un accouchement complique d'une grave hemorragie postpartum. La femme s'est presentee souffrant d'anemie, d'hypotension, de confusion mentale, de manifestations neuropsychiatriques, d'une posture anormale et d'une grave hyponatrernie. Des tests hormonaux ont revele un faible taux d'hormones pituitaires, des niveaux de cortisol et d'hormones thyro'idiennes sous Ia normale.Une imagerie par resonance magnetique du cerveau a indique Ia possibilite d'un SS. L'hyponatremie et !'apparition tardive de symptomes neuropsychiatriques sont une presentation peu commune du SS. Par consequent, lorsqu'une femme presente une amenorrhee secondaire et un defaut de lactation a Ia suite d'un accouchement ainsi qu'une apparition tardive de symptomes neuropsychiatriques et de l'hyponatremie, cela constitue un indice eleve d'un cas de syndrome de Sheehan.

42 Volu me 11, Is su e 3, 20 1 6 Ca n a d ia n Journal of Gene r al In terna l Medic in e

Bhattacharya et al.

Introduction

Sheehan syndrome (SS), or post partum necrosis of the pituitary gland, is a rare complication of post partum haemorrhage first described by H L Sheehan in 1937.1 It occurs as a result of ischemic injury to the anterior pituitary due to severe postpartum haemorrhage. Clinically, SS is commonly suspected in a woman with a history of post partum haemorrhage who develops failure of lactation and subsequent amenorrhoea. However, clinical manifestation may be subtle and variable, from asymptomatic cases to secondary amenorrhoea, lactational failure, neuropsychiatric manifestations like psychosis and seizures etc. Hyponatraemia is an uncommon presentation of this disease.2 The Authors report a case of SS presenting with late onset neuropsychiatric features characterized by a state of acute confusion and abnormal posturing, along with hyponatraernia, which is an uncommon presentation of this disease.

Case Report

A 30-year-old mother of three, presented to the emergency department with altered sensorium and abnormal posturing of the body for one day preceded by two episodes of convulsions. There was no history of fever, acute blood loss, intake of any drugs or illicit substances or bowel and bladder dysfunction.

Table 1:Showing laboratory findings in the patient with Sheehan's syndrome

She had pallor, hypotension (BP of 80/60mm Hg), with mild tachycardia (pulse rate - 102/rnin) and a respiratory rate of

20/min. She was conscious but disoriented, extremely restless

with hypertonia of all four limbs. There were no signs of meningeal irritation, papilloedma or focal neurological deficits. Examination of the other systems revealed no significant abnormalities.

Laboratory investigations (Table 1) showed severe

hyponatremia with hypochloremia, a low random blood glucose and moderate anaemia. The other electrolytes (potassium, calcium, bicarbonate) and renal functions were normal. Apart from mildly elevated hepatic transaminases, the liver function tests were normal. The chest x-ray and electrocardiogram revealed no abnormalities. Ultrasonography of the abdomen revealed mild collection in the uterine cavity and cholelithiasis (incidental). Cerebrospinal fluid analysis did not reveal significant abnormalities, except for occasional cells (lymphocytes <3/mm3 , glucose of 56 mg!dl, protein of

39.5 mg!dL and absence of any organism on gram stain and acid fast bacilli stain.On further enquiry, it was found that the patient gave birth to a child 13 months earlier, followed by severe post partum bleeding leading to shock which required six units of blood transfusion.During the post partum period, she had failed to lactate and developed amenorrhoea which was persisting.

Laboratory Parameter {units)

Report

Reference Values

Laboratory Parameter {units)

On Admission

At Discharge

Reference Values

Hemogram

Hemoglobin (gm/dl)

9.9

10.8

12-18

Total Leucocytic count (x1OlJmml)

7500

7600

4-11

Differential leucocytic count (%)

Neutrophil Lymphocyte Monocyte Eosinophil Basophil

66

27

04

03

00

68

25

04

03

00

4Q-75

20-45

2-10

1-6 s1

Platelet count (x1Ql/mm 3)

250

280

25Q-400

Erythrocyte Sedimentation rate (mm/h)

02

-

0-20

Biochemistry

Liver Function Test

Bilirubin (mg/dl) Total

Direct

Indirect

1.0

0.2

0.8

1.1

0.3

0.8

0.3-1.3

0.1-0.4

0.2-0.9

Al(lUIL)

106

88

7-41

AST (U/L)

39

40

12-38

Canadian Journa l of Genera l I nterna l Medic ine Volume 11, Issue 3, 2016 43

Sheehan's Syndrome Presenting with Hyponatraemia

ALP (lUlL)

56

58

30-120

TotalProtein(g/dL)

7.6

7.4

6.3-8.2

S.Aibumin(g/dL)

4.0

4.0

3.5-5

S.Globulin(g/dL)

3.6

3.4

1.5-3

Coagulation Profile

Prothrombin Time(s)

13.6

13.8

13.5

INR

1.01

1.02

APIT(s)

24

24

22-34

RenalProfile

Serum Creatinine(mg/dL)

0.8

0.9

0.8-1.5

Blood Urea (mg/dL)

16

18

10-5

Serum Sodium (mEq/L)

107

138

135-145

Serum Potassium (mEq/L)

5.2

3.9

3.5-5.5

Serum Calcium (mg/dL)

9.2

9.3

8.7-10.2

Serum Chloride (mEq/L)

86

106

90-110

Serum Bicarbonate (mEq/L)

23

24

22-28

Blood Glucose,Random (mg/dL)

79

108

70-140

Hormonal assays

TSH (IJIUimL)

1.01

.

0.34-5.60

FT3 (pg/mL)

0.79

2.5-3.90

FT4 (ng/dl)

0.46

.

0.61-1.12

Prolactin (ng/mL)

1.1

.

2-29

FSH (miUimL)

5.47

.

4.7-21.5

Growth hormone (ng/mL)

0.167

.

<10

Cortisol(Sam) (1Jg/dl)

3.6

.

7-28

Blood Culture

Sterile

.

.

Cerebrospinalfluid

Protein (mg/dL)

38

.

15-50

Glucose (mg/dL)

50

.

40-70

Chloride (meq/L)

120

.

116-122

WBC (0-5/u L)

0

.

0

RBC

0

.

0

Gram Stain

No pus cells or bacteria seen

.

.

AFB

Negative

.

.

India Ink stain

No encapsulated organism seen

.

.

Culture

Sterile

.

.

Urine Culture

Sterile

.

.

HIV 1,11

Non Reactive

.

.

HBsAg

Negative

.

.

Anti-HCV

Negative

.

.

ALT = alanme ammotransferase; AST = aspartate ammotransferase;ALP = alkaline phosphatase;INR = mternat10nal normalised rat1o;

APTT =activated partial thromboplastin time; TSH =thyroid stimulating hormone;FT3 = Free triiodothyronine;FT4 =free thyroxine; FSH =follicle stimulating hormone; AFB =acid fast bacillus,HIV = human immunodeficiency virus;RBC =red blood cell count;

WBC = white blood cell count

44 Vo lu me 11, Issue 3, 2016 Canad i an Journa l of Gene r a l I nter nal Medicine

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Bhattacharya et al.

Sodium replacement (both oral and intravenous 3% NaCl) was initiated and serial electrolyte monitoring of electrolytes was done, but there was persistent hyponatremia which was not being fully corrected even after adequate sodium supplementation. Further tests were carried out to investigate the cause of secondary amenorrhoea with persistent hyponatraemia. Hormonal assays (Table 1) showed low levels of serum free thyroxine (FT4), Human Growth Hormone, Prolactin and the 08.00 AM Cortisol levels below the normal range. The serum levels of TSH and FSH were near the lower levels of the normal range. Measurement of plasma ACTH and cosyntropin challenge test could not be done. Magnetic resonance imaging of the pituitary gland showed atrophy of the right part of the pituitary gland with increase in CSF signal intensity in the sella ("empty sella") (Figures 1 and 2).

With this clinical and laboratory findings, a diagnosis of SS with pituitary failure presenting with delayed onset neuropsychiatric manifestations and hyponatraemia was made. The patient was started on replacement therapy of corticosteroid (hydrocortisone and fludrocortisone), thyroxine and combined estrogen - progesterone oral contraceptive tablets. Initiation of replacement therapy lead to gradual correction of hyponatraemia and resolution of clinical symptoms. The patient was discharged and continues to maintain good health on subsequent follow ups.

Discussion

SS is characterized by ischemic anterior pituitary insufficiency usually preceded by postpartum haemorrhage (PPH). Enlargement of pituitary gland, small sellar size, disseminated intravascular coagulation and autoimmunity have been suggested to play a role in the pathogenesis of this disease. SS is characterized by varying degrees of dysfunction of the anterior pituitary.3 The anterior pituitary is supplied mainly by the portal venous system which is a low pressure system. Enlargement of pituitary cells, particularly the lactotrophs, occur during pregnancy but without a corresponding matching increase in vascular supply.4 So whenever the pituitary becomes vulnerable to hypo-perfusion in the post partum period, ischemic necrosis of the pituitary gland occurs. It is commonly suspected when the mother complains of failure or difficulty in lactation and amenorrhea following child birth.
SS can range from pan-hypopituitarism to selective hormone loses.5 The mean age at diagnosis is variable,6• ranging from 48.2±10 to 60.1±3.4 years. Our case presented at a comparatively younger age of 30 years. The time in years between the inciting delivery and diagnosis is variable,6 7 ranging from 13.9±6.1 to 26.8±2.5 years. However, our case had a much shorter time of presentation since inciting pregnancy of only 13 months. Thus, in our case, we see a more acute presentation in a younger patient, in comparison to

Figure 1. MR imaging of the pituitary gland in Sheehan syndrome. (A) Sagittal T1-weighted spin-echo images show atrophy of the right part of the pituitary gland (arrow).There is CSF signal intensity in the sella ("empty sella"). (B) Coronal gadolinium enhanced T1-weighted MR images reveal central low signal intensity and peripheral enhancement in the pituitary gland (arrow).

Figure 2. (A) Sagittal pre-contrast and (B) gadolinium enhanced T1-weighted MR images show central high signal intensity and peripheral enhancement in the left part of the pituitary gland (arrows).

Canadian Journal of Genera l I nterna l Medic ine Volume 11, Issue 3, 2016 45

Sheehan's Syndrome Presenting with Hyponatraemia

the usually more common delayed presentations of SS. Our patient was found to be moderately anemic. Anemia has been reported in as many as 63.8% of patients with SS in one study.8

Hyponatremia is a rare acute presentation of SS.2 9 10

Overall, the prevalence of hyponatraemia in cases of SS has been variable6 8 ranging from 21-32%. 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.U Severe hyponatremia leading to neuropsychiatric manifestations and acute confusional state as presenting symptoms Sheehan syndrome has been rarely described in the literature.12

Conclusion

Diagnosis of SS is often challenging and a high index of suspicion and clinical acumen is needed to diagnose this entity. Deficiency of various pituitary hormones and their target hormones produces a myriad of clinical features. MRI of the brain and pituitary fossa may show an empty sella or evidence of haemorrhage but is neither diagnostic nor mandatory.13

Keeping in view the varied clinical manifestation of SS, in

any woman with a history of post partum haemorrhage, who presents with a state of acute confusion and neuropsychiatric manifestations due to hyponatraemia, the possibility of SS should be kept in the differential diagnosis.

References

1. Sheehan HL. Postpartum necrosis of the anterior pituitary.J Path Bacteriol

1937;45:189-214

2. Boulanger E, Pagniez, D, Roueff S, Binaut R. Valat A S, Provost N et a!.Sheehan syndrome presenting as early post-partum hyponatraemia. Nephrology Dialysis Transplantation 1999; 14(11):2714-2715.

3. Kelestimur F.Sheehan's syndrome.Pituitary 2003;6:181-8.

4. Nussey SS, Whitehead SA. Endo- An integrated Approach.200I, Part

A-1257(under heading Sheehan's syndrome).

5. Ozbey N,lnanc S, Aral F, Azezli A, Orhan Y,Sencer E eta!.(1994). Clinical and laboratory evaluation of 40 patients with Sheehan's syndrome. Israel Journal of Medical Sciences 1994;30{11):826-29.

6. Sert M, Tetik T, Kirim S, Kocak M.Clinical report of28 Patients with

Sheehan's syndrome. Endocr J 2003; 50:297-301.

7. Dokmeta HS, Kilicli F, Korkmaz S, Yonem 0.Characteristic features of20 patients with Sheehan's syndrome. Gynecol Endocrinol 2006; 22:279-83

8. Gei-Guardia 0, Soto-Herrera E, Gei-Brealey A, Chen-Ku CH.Sheehan's

Syndrome in Costa Rica:Clinical experience on 60 cases. Endocr Pract 20 I 0;

1:1-27.

9. Shoji M, Kimura T, Ota K. Cortical laminar necrosis and central pontine myelinolysis in a patient with Sheehan syndrome and severe hyponatremia. Intern Med 1996; 35:427- 31.

10.Putterman C, Almog Y, Caraco Y, Gross DJ, Ben-Chetrit E. Inappropriate

secretion of antidiuretic hormone in Sheehan's syndrome:A rare cause of postpartum hyponatremia. Am J Obstet Gynecol1991; 165(5 Pt 1):1330-33.

11.Schrager, S., & Sabo, L. Sheehan syndrome:a rare complication of postpartum hemorrhage. The Journal of the American Board of Family Practice 2001; 14(5): 389-91.

12.Kurtulmus N,Yarman S. Hyponatremia as the presenting manifestation of

Sheehan's syndrome in elderly patients. Aging Clin Exp Res 2006; 18: 536-9

13.Dejager S, Gerber S, Foubert L,Turpin G. Sheehan syndrome differential diagnosis in the acute phase. J Intern Med 1998; 244:261- 266.

Conflict of interest:None

Sources of funding: Nil

46 Vo l ume 11 , Issue 3, 2016 Canad i an Journal of Genera l Interna l Med i c ine