Dr. Md.

Mamnur Rashid
MD (Neurology) Thesis Part Student
Dhaka Medical College
Role of Hypothalamus in the action
of nervous system
First-Head ganglion of ANS

Second- Circadian and seasonal clock

for behavioral and sleep-wake functions

Third- Maintain homeostasis and

participate in substructures of emotion and
affective behavior
Hypothalamic control of pituitary secretions

Almost all secretions by the pituitary are

controlled by either hormonal or nervous
signals from hypothalamus
Hypothalamic control of anterior pituitary secretions
n Hypothalamic Regulatory Hormones Effect on Ant Pituitary

1. Thyrotropin-releasing hormone (TRH) (+) TSH & Prolactin

2. Corticotropin-releasing hormone (CRH) (+) ACTH

3. Growth hormone releasing hormone (GHRH) (+) GH

4. Growth hormone inhibitory hormone (GHIH) (-) GH

“Somatostatin (SS)” (-) TSH

5. Gonadotropin-releasing hormone (GnRH) (+) Gonadotropic hormones

(LH, & FSH)

6. Prolactin releasing hormone (PRH) (+) Prolactin

7. Prolactin releasing inhibitory hormone (PRIH) (-) Prolactin

“Dopamine”
Hypothalamic control of posterior pituitary
secretions
 Diseases involving hypothalamus
Structural:

Infiltrative and inflammatory diseases

 Tuberculosis
 Sarcoidosis
 Encephalitis
 Meningitis
 Langerhans cell histiocytosis
Diseases involving hypothalamus (cont…)

Space occupying lesions

 Pituitary adenoma
 Craniopharyngioma
 Metastasis
 Lymphoma and leukaemia
 Hamartoma
 Glioma
 Meningioma
 Hemangioblastoma
 Cysts : Epidermoid, dermoid.
Diseases involving hypothalamus (cont.)

Vascular
 Stroke
 Arterio-venous malformation
 Aneurysm

Iatrogenic
 Para-sellar surgery
 Cranial irradiation
 Diseases involving hypothalamus (cont.)

Miscelleneous
 Head injury
 Hydrocephalus
 Wernicke’s encephalopathy
Developmental Disorder
Septo-optic dysplasia
Kallmann’s syndrome
Diseases involving hypothalamus (cont.)

Functional abnormalities

Isolated hormone or receptor defect

 Systemic illness
 psychosocial deprivation
 Anorexia nervosa
 Excessive exersize
 Hypothalamic syndromes
Global hypothalamic syndromes:
 Disordered One, all or many hypothalamic
functions,
often with signs of disease in contiguous
structures
i.e- Hypo-pituitarism

Partial hypothalamic syndromes :

Deficiency or overproduction of a single
hormone
Attributable to discrete lession
i.e-Cranial DI,SIADH
 Hypothalamic dysfunction

Non-endocrine: Endocrine:

Temperature regulation Hypothalamo

Appetite/Eating behavior -pituitary unit
Emotion& libido Hypo/
Biological rhythm hyperfunctio
Mechanical effect n of-
Optic Anterior
chiasma
compression pituitary
Posterior
Hydrocephalus
pituitary
 Endocrine dysfunctions
Hypo-functions
Anterior Pituitary:
Growth hormone deficiency
Hypothalamic hypogonadism
Secondary hypothyroidism
Pan-hypopituitarism

Posterior Pituitary:

Cranial diabetes insipidus

 Endocrine dysfunctions (cont…)

Hyper-functions
Hypothalamic precocious puberty
Hypothalamic hyper-prolactinaemia
Syndrome of inappropriate ADH secretion(SIADH)
 Endocrine dysfunctions (cont...)

Growth hormone deficiency due to hypothalamic

disorder are mostly functional :

 Congenital idiopathic growth hormone deficiency

 Emotional deprivation
 GH deficiency in chronic illness
 Endocrine dysfunctions (cont.)
Hypothalamic hypogonadism
Cause

 Isolated GnRH deficiency(Kallmann’s syndrome)

 Structural lesion of hypothalamus
 Hyper- prolactinaemia
 Endocrine dysfunctions (cont.)

Cranial diabetes insipidus

Pathogenesis:

Lack of ADH
Impaired renal water reabsorption
Diuresis
Raised plasma osmolarity
Increased thirst
 Endocrine dysfunctions (cont.)
Cranial diabetes insipidus
Cause

 Para-sellar surgery
 Head injury
 ICSOL
 Neuro-sarcoidosis
 Idiopathic
 Genetic(AVP gene mutation, DIDMOD syndrome)
 Endocrine dysfunctions (cont.)
Cranial diabetes insipidus
Investigation
Water deprivation test :
 Plasma osmolality > 300 mOsm/Kg
 Urine osmolality < 600 mOsm/Kg
> 50% improvement after DDVAP
 Endocrine dysfunctions (cont.)
Hypothalamic hypergonadism
Cause
 Structural lesion of hypothalamus
(Hamartoma most common)
 Idiopathic
More common in females (most are idiopathic)
Males are more severely affected (most are
structural lesions)
 Endocrine dysfunctions (cont.)
Syndrome of inappropriate ADH secretion
(SIADH)

Pathogenesis
Excessive ADH
Excessive water reabsorption in collecting tubule
Dilutional hyponatraemia
 Endocrine dysfunctions (cont.)
SIADH (cont.)
Cause

CNS disorders : Stroke, infection, injury

Pulmonary disorders : Pneumonia, TB ,Br Ca.
Drugs : Carbamazepine, TCA, Antipsychotic
Idiopathic
 Endocrine dysfunctions (cont.)
SIADH (cont.)
Diagnosis
 Low plasma sodium (<130 mmol/L)
 Low plasma osmolality (<270 mmol/kg)
 Urine osmolality not minimally low (> 150
mmol/kg)
 Urine Na not minimally low (>30 mmol/L)
 Exclusion of other causes
 Appropriate clinical setting
Endocrine dysfunctions (cont.)
SIADH (cont.)
 Management:

Water restriction
Address of appropriate clinical conditions
Demiclocycline & Urea
Vaptans
 Neurogenic (Cerebral) salt
wasting(Nelson syndrome)
 Moderate reduction of sodium in-
 acute intracranial disease (SAH, head injury,
cerebral tumor) and
 post operatively in neurosurgical patients

 In recent years, it has been recognized that this

condition is a result of natriuresis and not due to
water retention caused by ADH secretion.
ANP (Cardiac atria, Surrounding the 3rd ventricle in
ventral hypothalamic region)

Fluid restriction with the intention to treat SIADH can

have dangerous result
 Non-Endocrine dysfunction
Disturbance of temperature regulation
Hyperthermia :Tem 41◦C(106◦F) or higher

Lesion in Pre-optic- Anterior hypothalamus

 Impairment of dissipate heat adequately

Vasodilatation

Sweating
Disturbance of temperature regulation(cont…)
Hypothermia : Tem 33◦C or less

Lesion in Posterior hypothalamus

Impairment of heat production adequately

Vasoconstriction
Severing

Shapiro’s syndrome
Reverse Shapiro’s syndrome
Disturbance of temperature
regulation(CONT…)
 Spontaneous periodic hypothermia

Episodically there may be autonomic disturbance like

salivation, nausea, vomiting, sweating, vasodilatation,
lacrimation and bradycardia.

Per- rectal temperature fall to 30 0C, seizure may

occur.

 Between attacks, temperature regulation is normal.

Associated with cholesteatoma of the 3 rd ventricle and

with agenesis of the corpus- callosum
 Disturbance of body weight
Hypothalamic obesity :Bilateral Lesion in
 Ventro - medial hypothalamus: Satiety center

Hypothalamic weight loss: Bilateral Lesion in

 Ventro-lateral hypothalamus: Appetite center

Most reported cases: Due to

 Tumors- Craniopharyngioma
 Trauma
 Inflammatory disease
 Hydrocephalous
 Froehlich syndrome

Obesity and hypogonadism occur together or

separately, often combined with loss of vision
and unprovoked rage, aggression or antisocial
behavior. DI may be added.

Usual causes are –Craniopharyngioma

-glioma
 Disturbance of body weight(cont…)
Anorexia nervosa & Bulimia nervosa

Alteration of several hypothalamic functions-

Appetite
Temperature control
Menstruation
Cause:
Not usually due to primary dysfunction of
hypothalamic nuclei
Secondary to extreme weight loss
Hypothalamic tumors
Acute Autonomic Crises ("Sympathetic
Storm")
Three separate mechanisms of the
hypersympathetic state are observed at different
times after the head injury or cerebral
hemorrhage:

Adrenal catecholamines release

Brainstem-mediated vasopressor reaction (Cushing

response)
Several minutes' duration of rigid extensor
Cardiovascular disorders with
hypothalamic lesions

Byer and colleagues describe in patients with

stroke.
Large upright T wave and prolonged QT intervals

Acute lesions of brain particularly with SAH and

head trauma
SVT
Ventricular ectopic
Ventricular fibrillation
 Gastric hemorrhage

Lesions: in or near the tuberal nuclei

Superficial erosions or ulcerations of the

gastric mucosa in the absence of
hyperacidity( cushing ulcer).

Seen in patients with several types of acute

intracranial disease.
 Neurogenic pulmonary oedema
Lesion: Caudal hypothalamus

Massive pulmonary oedema could be-

 Head injury
 SAH
 ICH
 Bacterial meningitis
 Status epilepticus.
Neurogenic pulmonary oedema(cont..)
Sudden elevation of ICP

Extreme systemic hypertension without obvious

Left ventricular failure

Massive pulmonary oedema

Neurogenic rather than a cardiogenic cause.

Disorders of consciousness and personality
Acute lesions in the posterior and lateral parts
of hypothalamus may be

Associated with stupor

Chronic hypothalamic lesions may be

Accompanied by drowsiness, confusion or no

mental changes at all.
Approach to hypothalamic-pituitary
dysfunction
Structural/Site of
lesion Functional problem
 Endocrine
&Non-endocrine Hyper- function
dysfunction &hypo- function of
anterior &posterior
Hypothalamic
pituitary hormones
lesion
Endocrine
dysfunction only

Pituitary lesion
Approach to hypothalamic-pituitary
dysfunction(cont…)
Endocrinological Structural
Not every patient requires full MRI- With
battery of pituitary test gadolinium
No single endocrine test can contrast detect
provide all the answers about hypothalamic and
pituitary function pituitary lesion
Stimulator & suppressor test about 82%-94%.
 Developmental disorders
Developmental abnormalities of Skull and brain
can cause Hypopituitarism (varying degree)

Septo-optic dysplasia:

Affected children have mutations in the HESX1 gene

Agenesis of septum pellucidum

Hypoplastic optic nerve
Hypothalamic pecocious puberty
Cleft palate, syndactyly, ear deformities, hypertelorism,
optic atrophy and anosmia.
Developmental disorders (cont.)
Kallmann’s syndrome
X-linked recessive

Clinical features
 Hypogonadism
 Anosmia
 Tall stature
 Mental retardation,Deafness, colour blindness

Investigation
 Low GnRH, LH, FSH, testosterone
 MRI : Hypoplastic or absent olfactory bulbs
 Craniopharyngioma

Origin : Remnants of Rathke’s pouch

Cystic supra-sellar mass

Presentation:
 Raised ICP
 Visual field defect
 Hypopituitarism(90%), DI(10%)
 Hydrocephalus
Craniopharyngioma (contd)
 Neurosarcoidosis
Neurosarcoidosis occurs in 8% cases.

Presentation
Meningitis
Cranial nerve palsy
Hypothalamic dysfunction : DI
 Sarcoidosis (cont.)
Investigations

 Chest X-ray
 Serum calcium
 Serum ACE
 Histopathology/cytology
 CSF study (including ACE level)
 MRI brain