Sheehan's Syndrome

1. SHEHAN’S SYNDROME
Presented by
 DR WASEEM H. MIRZA
 1ST YEAR PG, DEPT OF MEDICINE
 GOVT. MEDICAL COLLEGE, SRINAGAR

2. Anatomy of the pituitary gland.
 Pea-sized oval structure, suspended from brain by infundibulum(P. stalk)
 Anteriorly – Sphenoid sinus
 Posteriorly – Posterior intercavernous sinus, the basilar artery and the pons.
 Superiorly – Diaphragma sellae and optic chiasma.
 Inferiorly – Sphenoid sinus
 Laterally – Cavernous sinus.

4.  Lobes
 Anterior Lobe
1. Pars anterior – the largest part, responsible for hormone secretion.
2. Pars intermedia Not developed in human
3. Pars tuberalis encloses infundibulum
 Posterior lobe(neurohypothysis)
1. ADH, oxytocin

5. vascularization of the pituitary gland.

6.  The infundibulum, the median eminence, pars tuberalis by superior hypophyseal artery
 Posterior lobe by the inferior hypophyseal artery arising from the meningohypophyseal trunk(ica)
 Pars distalis has unique circulation to receive hormones from the hypothalamus and the posterior
pituitary gland, besides substances from peripheral circulation but makes it vulnerable to ischaemia
due to hypovolemia and hypotension during the postpartum period. It receives very little to no
arterial blood supply.
 Instead, mainly supplied by the venous system;
Long portal veins from the portal capillary system in the median eminence.
Short portal vessels from post pituitary.

8. Pituitary hormones
Hypothalmic Releasing and inhibiting factors
Anterior pituitary hormones
Target organ/ Target hormones
 Neg feedback control
 Oxytocin +ve feedback

10. Pituitary gland enlargement in pregnancy
 Increase hormones demand.
 Normal height on MRI is 4-8 mm.
 45% enlargement during the first trimester
 120–136% of its original size near term and its highest volume during the first
few weeks of the postpartum period and regain its normal size, shape and
volume within 6 months following delivery.
 Increased demand and compression of the vasculature of the gland.
 Increase vulnerability to Ischemia, due to PPH
 That’s why shehan’s syndrome is due to hypovolemia as result of PPH not due to
other causes.

11. Epidemiology
 Pituitary tumours and their treatments are the most common causes of hypopituitarism (~60%)
and ~30% of hypopituitarism cases have a non-tumour origin. Sheehan syndrome explains 6% of
all causes of hypopituitarism.
 Rare in developed world due to modern improved obs care.
 Common in developing countries, For example, in Kashmir, India, the prevalence of Sheehan
syndrome was estimated to be ~3.1% of parous women ≥20 years of age; ~63% of the women
with Sheehan syndrome in this study had given birth at home.

12. Shehan’s syndrome
 1St described by Shehan in 1937.
 Deficiency of anterior pituitary hormone resulting from infarction and necrosis of
the physiologically enlarged pituitary gland of pregnancy, usually preceded by
postpartum hemorrhage (PPH) which leads to arterial spasm in smaller vessels,
apoplexy and subsequent pituitary necrosis.

13. Mechanisms of Sheehan syndrome
 The pathogenesis of Sheehan syndrome remains uncertain. Not every patient has a history of massive PPH
nor does every massive PPH lead to Sheehan syndrome.
 confounding factors that affect the initiation and progression of the disease, which require further
investigation:
1. severity and spread of necrosis;
2. age of the patient;
3. history of previous births associated with PPH;
4. number of births.
5. ?Autoimmune component.
6. ?genetic predisposition

14. Risk factors.
 Restricted pituitary blood supply following untreated severe hypotension associated with pph is the most
common cause for the development of shehan’s syndrome.
 Massive PPH (>2000ml ) may be predictive for developing Sheehan syndrome.
 Predisposing factors for restricted pituitary blood supply
1. Pituitary gland enlargement
2. Small size sella turcica: Mean sella turcica volume in patients (mean ± SD = 340.5 ± 214 mm³). Healthy women
(mean ± SD = 602.5 ± 192 mm³),
3. Arteriolar vasospasm due to hypotension,
4. Thrombosis and coagulation abnormalities. frequency of genetic mutations of coagulation factor V, II
methylenetetrahydrofolate reductase (MTHFR*C677T and MTHFR*A1298C) and plasminogen activator inhibitor
type 1 (PAI1; also known as SERPINE1), is increased in patients with Sheehan syndrome compared with the general
population.
 Sheehan syndrome may also develop despite the rapid correction of hypovolemic shock and DIC

15. Disease initiation.
 The initial insult is necrosis of the anterior lobe due to infarction/arrest of blood flow/vasospasm/
thrombosis/arterial compression.
 Depending on the size and site of necrosis; pituitary hypofunction resulting in deficiency of hormones.
 If >50% of pituitary gland remains intact; function intact
 if >70% is affected; partial or panhypopituitarism

16. Disease progression.
 commonly characterized by slow progression of pituitary dysfunction, even several years after the
initial insult
 Autoimmune process : AutoAbs against pituitary & hypothalamus in patients. ?Cause/Consequence.
 Sequestered antigens due to tissue necrosis could trigger autoimmunity and may cause delayed
hypopituitarism.
 Percentage of cells that express both CD3 and DR1, is suggestive of an ongoing inflammation
accompanying the slow progression of pituitary dysfunction.

18. Characteristics of pituitary necrosis.
 Adenohypophysis cells were replaced by necrotic debris, coagulated blood,
inflammatory cells and ghost cells > scar > atrophy(empty sella).
 Somatotropic and lactotroph cells, located in the lateral wings, receive blood
supply only from the portal circulation are completely lost. Because of this, an
absence of PRL rise after TRH was considered to be the most sensitive screening
test.
 Gonadotropic cells which are scattered throughout the pituitary and
corticotrophs may be preserved.

19. Clinical manifestations
 Patients can present with symptoms ranging from isolated hypopituitarism to panhypopituitarism.
 GH and PRL are the most commonly affected hormones causing fine wrinkling around mouth and
lactation respt.
 FSH and LH deficiency leads to amenorrhoea/oligomenorrhoea/loss of libido.
 TSH loss can cause weight gain, constipation, cold intolerance etc
 ACTH loss can cause weakness, fatigue, weight loss, hypotension and hypoglycaemia.
 Posterior lobe can also be affected rarely, leading to diabetes insipidus.
 Sheehan syndrome can also result in severe clinical outcomes (such as adrenal crisis, circulatory collapse,
myxoedema coma and hyponatraemia) and can lead to death if not properly treated.

20. (a) Facial features of Sheehan’s syndrome showing fi ne wrinkling
of face, loss of eyebrows laterally, skin hypopigmentation. (b) T1-weighted
sagittal MRI image showing pituitary gland fi lled with cerebrospinal fluid and
stalk touching the base of floor features indicative of empty sella

21. Laboratory findings
Endocrine abnormalities.
 To show cortisol and GH deficiencies, Insulin tolerance test and a glucagon stimulation
test can be used.
 ACTH stimulation test
 FSH and LH levels are not increased to postmenopausal levels and LH levels do not
increase following GNRH stimulation test.
 TSH can be N,L or H. T4 is low. TRH test Neg.

22. Electrolyte abnormalities.
 Hyponatraemia is the most common.
 Other abnormalities are hypokalaemia, hypomagnesaemia, hypocalcaemia and
hypophosphataemia.
 Low cortisol
Low BP, Cardiac Output Inc CRH
Increase ADH

23. Haematological abnormalities.
 Anaemia (45–87%), thrombocytopenia (63–105%), pancytopenia (15%) and coagulation disorders.
 Anaemia: normochromic normocytic, can be hypochromic microcytic or rarely macrocytic.
 Cortisol and thyroid hormone def > decreasing the synthesis of erythropoietin or by decreasing the
biological effects of endogenous erythropoietin> Anaemia.
 Bone marrow hypoplasia and pancytopenia can occur; both are reversed after the replacement of deficient
hormones.
 Coagulation disorders can be diagnosed by measuring adaptive factor VIII and von Willebrand factor
deficiencies, decreased prothrombin time and activated prothrombin time, and an increase in the levels of
fibrinogen and d-dimer

24. Diagnostic criteria for
Sheehan syndrome

27. Differential diagnosis
 Pituitary tumours are the most common cause of hypopituitarism
 lymphocytic hypophysitis
 Pituitary apoplexy around the peripartum period

29. Prevention
 WHO guidelines for the prevention of PPH, which include a combination of interventions,
such as
1. cord clamping and cutting (within 1–3 minutes);
2. controlled cord traction ;
3. use of an uterotonic agent such as oxytocin, misoprostol.
 Anaemia during pregnancy should be corrected.
 Minimum interventions during delivery.

30. Management

31. Glucocorticoid replacement
 Acute adrenal insufficiency: Glucocorticoid treatment should be started immediately after taking a serum
sample for the measurement of cortisol and ACTH levels.
 dose should be titrated as per clinical findings instead of laboratory results
 To approximate the circadian rhythm of endogenous cortisol production dual-release hydrocortisone tab
given once daily.
 Lifelong therapy.
 Patients should be informed about increasing their daily dose in some situations such as infection, surgery
and trauma.

32. Thyroid hormone replacement
 Levo thyroxine should be given (75-150 mcg)
 Titration of dose depends on fT4 and fT3 levels rather than on TSH levels
 When hypothyroidism and hypoadrenalism occur together, thyroid hormone therapy should follow
glucocorticoid replacement to avoid adrenal crisis
 GH therapy increases conversion T4>T3, thus inceasing LT4 dose requirement.

33. Oestrogen and progesterone
replacement
 Controversial
 Replacement therapy is usually recommended in premenopausal women with Sheehan syndrome,
unless there is a contraindication (DVT, PE, severe cirrhosis, active viral hepatitis and uncontrolled
severe hypertension)
 Oral estrogen should be avoided in patient on GH therapy.

34. GH replacement
 Opinions about efficacy and the routine use of GH treatment are divided because of the risk–
benefit ratio and cost-effectiveness
 Different trails show beneifits of using GH such as improved body composition and the lipid profile,
improved cognitive function, improves sympathetic tone without an obvious arrhythmogenic
effect.
 Failed to improve the abnormal sleep patterns in Sheehan syndrome(more NREM less REM)
 Hydrocortisone dose may need to be increased after GH treatment in patients with GH deficiency.

35. Pregnancy and lactation
 Ovulation induction can be used in women who want to become pregnant, although some
patients can have spontaneous pregnancies. When pregnant, regular follow-up to adjust
glucocorticoid doses is needed.
 Levothyroxine doses also need adjustment.
 GH therapy should be stopped.
 There are no data about the replacement of PRL during gestation and the postpartum period for
lactation in PRL-deficient patients

36. Quality of life
 Most patients with Sheehan syndrome have nonspecific symptoms, such as
weakness, cold intolerance, anaemia and feeling unwell, which affect QOL,
especially because of long diagnostic delay. These patients can remain
undiagnosed or misdiagnosed for a long time and receive inappropriate
treatments.
 Increased awareness of this condition will result in earlier diagnosis and hence
better QOL, and lower morbidity and mortality.

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