DETAILED PRESENTATION ON PAN HYPOPITUITARISM AND SHEEHAN'S SYNDROME

1. HYPOPITUITARISM
&
SHEEHAN’S SYNDROME
DR. JYOTIRMAY MAJI
JR1, MD (GENERAL MEDICINE)
RKMSP & VIMS

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Another 28 years old female presenting with no menstruation for last 3 years and galactorhoea for 1 month.
No H/O recent child birth, no offending drug history, no pregnancy at present.
TSH normal, FSH, LH level low, MRI shows Empty Sella.

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BASIC ANATOMY & PHYSIOLOGY OF PITUITARY GLAND
Posterior Pituitary i.e. Neurohypophysis has two
types of neurons
a) Magnocellular- AVP & Oxytocin secretors
b) B) Parvocellular- Hypophysiotropic Secretors

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Gonadotrophs GP PP Somatotrophs
Thyrotrophs GP PP Corticotrophs Apears at 8 weeks
Lactrorophs Appears at 12weeks
PP

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PITUITARY TRANSCRIPTION FACTORS
• Prop 1- l/t Enlarged Pituitary Gland
• Pit 1
• T pit
• Six 6
• HESXL
• PitX2
• LHX3, LHX4
• SOX2, SOX3 – l/t Mental Retardation

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CAUSES OF PITUITARY INSUFFICIENCY

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Harrison 21st Edition

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INHERITED PITUITARY DEFICIENCY
• Receptor Defect- Leptin Receptor Mutation
Hyperphagia, Obesity, Central Hypogonadism
Decreased GnRH l/t attenuated FSH,LH
• Structural defect- Prader-Willi Syndrome (Maternal Disomy)
Deletion of Imprinted copies of Paternal SNRPN Genes, NECDIN Gene, Other Genes in Ch. 15q
(SWORP Gene)
Hypogonadotropic Hypogonadism, Mental Retardation, Adult Onset DM, Hyperphagia-Obesity,
C/C Hypotonia
• Hormone Mutations / Transcription Factor Defects-
a) HESX1 mutation- Septo optic Dysplasia- Dysgenesis of Septum Pellucidum or Corpus Callosum-
DI,GH Defficiency, Short Stature
b) PROP1 & Pit-1 mutation l/t GH, PRL, TSH, Gonadotropin mutation (Anterior Pituitary Lineage
deficiency)- CPHD
c) TPIT Mutation l/t ACTH deficiency & Hypocortisolism

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ACQUIRED HYPOPITUITARISM

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Traumatic
• Surgical Resection
• Radiation Damage
• Traumatic Brain Injury- ADH secretion reduced- High Osmolality with High Na+
Infiltrative/Inflammatory
• Sarcoidosis
• Lymphocytic histiocytosis- Hyperprolactinemia with diffuse Enlargement of Pituitary
• Drug Induced( Anti CTLA4 & Anti PD-1/PD-L1)
Infections
• TB, Pneumocystis, Histoplasmosis, Aspergillosis, Toxoplasmosis, CMV
Vascular
• Pituitary Apoplexy- Acute Intrapituitary Haemorrhagic event
• Spontaneous pituitary Shock, Sickle Cell Crisis, DM, HTN
adenoma infarction

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Pituitary Apoplexy may present with Hypotension, Shock, Severe Hypoglycaemia, CNS Haemorrhage,
Severe Headche,Meningeal Irritation, B/L Visual Changes, Opthalmoplegia, LOC, CVS Collapse
Treatment of Pituitary Apoplexy
1. Surgical Decompression to relieve ICP, Visual symptoms
2. I/V Glucocorticoids at high dose

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SHEEHAN’S SYNDROME
i. Postpartum
ii. Acquired factor VIII and von
Willebrand factor (aFVIII–VWF)
deficiency
iii. Shorter prothrombin time (PT)
and activated partial
thromboplastic time (aPTT),
higher fibrinogen and d-dimer
levels
iv. Anti-Pituitary antibodies (APAs)
v. Hypothalamic cell anti-
hypothalamus antibodies (AHAs),
but not against arginine
vasopressin AVP-secreting cells
vi. Anaemia, Pancytopenia,
Thrombocytopenia
vii. Increased Thrombophilic Genetic
Mutations

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Hormones Treatment
GH Deff.
Evoked GH<3 ng/ml, Low/Lowish
IGF-1, MPHD, increased ldl
Increased body fat, decreased
lean body mass, reduced muscle
mass, impaired CVS function
GH SupplementationTSH
TSH Deff. Catabolism, BMR, Growth, Brain
Dev. Problems, Hyponatremia
LT4 Supplementation
ACTH Deff.
(secondaey Adrenal Insufficiency)
Stress Hormone
Fatigue, weakness, anorexia,
N&V, occasionally Hypoglycaemia
Cortisol preferred
Increase dose in stress
FSH/LH Delayed puberty, Secondary
Gonadal Failure, infertility
For Males-Testosterone, FSH &
HCG
In Female- Estradiol, Beta HCG,
GnRH
Vasopressin Diabetes Incipidus Intransasal Desmopressin

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ACKNOWLEDGEMENTS:
• Faculties: Dr. Ajitesh Roy, Dr. Partha Sarathi Chowdhury , Dr. Pradeep Chakaraborty Sir, Dr.
Sujata Mazumdar
• Dr. Dilsad Khan, Dr. Debasish Das, Dr. Santu Biswas, Dr. Satyaki Mitra, Dr. Suryasish Dey &
other colleagues, seniors and juniors
• My Patients
• Harrison’ s Textbook Of Internal Medicine 21st Edition
• Postgraduate Medicine by Dr. Gurpreet S. Wander
• Nature Reviews Disease Primers
• Shivaprasad C. Sheehan's syndrome: Newer advances. Indian J Endocrinol Metab. 2011 Sep;15 Suppl 3(Suppl3):S203-
7. doi: 10.4103/2230-8210.84869. PMID: 22029025; PMCID: PMC3183525.
• González-González JG, Borjas-Almaguer OD, Salcido-Montenegro A, Rodríguez-Guajardo R, Elizondo-Plazas A, Montes-
de-Oca-Luna R, Rodríguez-Gutiérrez R. Sheehan's Syndrome Revisited: Underlying Autoimmunity or Hypoperfusion? Int
J Endocrinol. 2018 Feb 26;2018:8415860. doi: 10.1155/2018/8415860. PMID: 29681937; PMCID: PMC5846385.