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PATHOLOGY OF
HYPOTHALAMIC-PITUITARY
AREAS
Department of Internal Medicine №2
as.-prof. Martynyuk L.P.
Plan of
lecture
1.
2.
3.
4.
5.
6.
7.
8.
Anatomy and physiology of
hypothalamus and pituitary gland.
Classification of hypothalamus and
pituitary gland.
Etiology of hypothalamo – pituitary
disorders.
Acromegaly, giantism: diagnostic
criteria and treatment
Pituitary dwarfism: diagnostic criteria
and treament.
Hypopituitarism: diagnostic criteria and
treatment.
Diabetes insipidus: diagnostic criteria
and treatment.
Inapropritiative secretion of
vasopresin: diagnostic criteria and
treatment.
Plan of
lecture
9.
10.
11.
12.
13.
14.
-
Epidemiology of obesity.
Health consequences.
Etiology of obesity.
Predisposing factors of obesity.
Classification of obesity.
Clinical manifestations of obesity:
Alimentary obesity.
Hypothalamic obesity.
Pickwickian syndrome.
Barrakcer – Simmons’s disease
(progressing lipodystrophia).
Dercum’s disease (generalized painful
lipomatosis.)
Babinsky-Frelych’s disease (adiposegenital dystrophy).
Lorens – Moon – Bydlya’s syndrome.
Morganyi – Stuart – Morel’s syndrome.
Postnatal neuroendocrine syndrome.
15. Treatment of obesity.
The pituitary gland is the “master gland”, which lies
in a bony structure, the sella turcica, located at the base of the
skull. The gland is a small organ about I cm long; it weighs 500
mg and is divided into two parts, anterior (adenohypophysis)
and posterior (neurohypophysis).
The anterior pituitary secretes
- corticotropin (ACTH)
- Prolactin
- Somatotropin (growth hormone (GH)
- gonadotropins [follicle-stimulating (FSH)
and luteinizing (LH) hormones]
- thyrotropin (TSH)
- melanocyte-stimulating hormones (MSH).
In the nerve endings of the posterior pituitary are
stored
- Vasopressin (antidiuretic hormone, ADH)
- Oxytocin
The hypothalamus plays an important role in
hormone regulation by secreting a series of small peptides
which stimulate or inhibit the synthesis and release of
hormones by the anterior pituitary
• First hypothalamic releasing hormone identified in
1970 was TRH by Schalli and Guilemin who von
Nobel prize in medicine for their discoveries in1977
• Realising
Inhibiting
-
CRG
TRG
LGRG
FSRG
GRH
PRG
MRG
- GIH (somatostatin)
- PIF (dopamine)
- MIH
Regulation
• FEEDBACK:
Hormone secretion → delivery to target
cells → hormone recognition by receptors
in target cells → biologic effect →
hormone degradation → signal from target
cells to stop further hormone secretion
Regulation
Etiology of hypothalamo –
pituitary disorders
1.Trauma
2. Infectious diseases:
- acute (scarlet fever, influenza)
- chronic (tuberculosis, malaria, toxoplasmosis)
3. Tumor or metastasis
4. Vascular damaging (thrombosis, thromboembolia)
5. Metabolic disorders (xanthomathosis)
6. Congenital pituitary hypo – or aplasia (syndrome of
“empty sella turcica”
7. Genetic predisposition
8. Idiopathic
Classification
of hypothalamo – pituitary disorders
•
Adenohypophysis disorders
1. Secretion of GH
overproduction: acromegaly, giantism
dificiency: pituitary dwarfism
2. Secretion of ACTH
overproduction: Cushing’s syndrome, hypothalamic syndrome
3. Secretion of Prolactin
overproduction: hyperprolactinemia, galactorhea-amenorhea
4. Secretion of TSH
5. Secretion of Gonadotropines: adiposogenital-dystrophy
6. Hypothalamic obesity
•
Neurohypophysis disorders
1. Deficiency of vasopressin: diabetes insipidus
2. Inapropritiative secretion of vasopressin
GROWTH-HORMONE EXCESS
(acromegaly and gigantism)
Chronic, debilitating disorder resulting from
exessive secretion of GH and resulting in
production of insulin-like growth factor 1 (IGF-1),
which lead to typical picture: gigantism before
puberty and to acromegaly after puberty.
Pharmacologic therapy
1. A dopaminergic agonist and ergot derivative,
2a-bromergocriptine (bromocriptinef 10 to 60
mg/day, (clinical remissions in 73 % patients,
normalization of GH level in 22 % of patients).
Side effects include nausea, orthostatic hypotension, constipation, digital vasospasm, and peptic ulcer.
2. Comatostatin analogues: octreotide,
sandostatin (clinical remissions in 90 % patients,
normalization of GH level in 50 % of patients).
Side effects include nausea, diarrhea, gallstones, glucose
intolorence.
Surgery:
Treatment
- Transsphenoidal hypophysectomy is the procedure of
choice.
Advantages: effectivity in nearly 90 % of the patients, simplicity
and low morbidity.
Side effects: hypupituitarism, diabetes insipidus, recurrence of symptoms.
- Craniotomy is reserved for large tumors with
suprasellar extension and involvement of the optic
chiasm.
- Cryohypophysectomy (destruction of the pituitary by
cold injury) can reduce the secretion of GH (without
causing hypopituitarism) in 88 % of the patients.
External irradiation:
- External beam
- Gamma knife
PITUITARY DWARFISM
(GROWTH FAILURE) it is the disease caused by decreased
secretion of GH by pituiatary gland or
decreased sensitivity of peripheral tissues to
this hormone and leads to growth
retardation.
Treatment.
I.
II.
III.
1.
2.
3.
4.
5.
IV.
Balanced diet.
Complex of physical exercises.
Pharmacotherapy.
GH (synthetic).
Anabolic steroids under the control of biologic (osteal)
age.
Thyroid replacement.
Replacement with gonodal steroids is never indicated until
puberty normally occurs. These agents in high doses can
hasten bone maturation and epiphyseal closure, thereby
limiting the height which may ultimately be reached.
Vitamintherapy.
Surgical therapy (a craniopharyngioma presents special
therapeutic problems, usually necessitating removal of
tumor tissue or drainage of fluid from tumor cysts.
HYPOPITUITARISM
It is the syndrome, which is characterized
by deficiency of one or more anterior
pituitary hormones.
Treatment
- eliminating the underlying cause
- replacing the deficient hormones
- Pituitary tumors should be removed surgically,
although irradiation and drug therapy (bromocriptine)
are also available.
- Treatment of acute and chronic infection
Hypothalamic peptides or pituitary hormones are not suitable for
hormone replacement : (1) The human hormones are difficult to
oblain in pure form; (2) because of their nature and short halhlife they have to be given parenterally and frequently; (3) since
they stimulate antibody formation, their activity is lost a few
weeks after initiation of therapy.
Under these circumstances the usual practice is to administer the
hormones produced by the target glands. They are available in
pure form and are relatively inexpensive.
Replacement therapy
• Hydrocortisone 20 - 30 mg/day, prednisolone 5 - 15
mg/day
• Replacement with gonodal steroids is never
indicated until puberty normally occurs. These
agents in high doses can fasten bone maturation
and epiphyseal closure, thereby limiting the height
which may ultimately be reached.
- In males testosterone therapy is recommended.
- Premenupausal females with ovarian failure should
be treated with estrogens.
• Thyroid drugs (L-thyroxin, euthyrox)
• Vitamines, anabolic hormones
DIABETES INSIPIDUS
is a clinical disorder characterized by
the excretion of large quantities of diluted urine
and caused either by failure of ADH release
(hypothalamic diabetes insipidus) or by
lack of response of the tubules to normal quantities
of circulating ADH (nephrogenic diabetes
insipidus).
Psychogenic
polydipsia
Hypothalamic
diabetes insipidus
Nephrogenic
diabetes insipidus
History
Insidious onset
Abrupt onset, brain
surgery,
tumor
present,
steroid
therapy
Family
history,
chronic
hypokalemia,
chronic
hypercalcemia,
postanesthesia
Physical
examination
Normal hydration
Dehydration
be present
may Dehydration
be present
may
Laboratory:
270 – 290 (↓ to N)
- serum osmolality; < 200 (↓)
- urine osmolality
285 – 320 (N to ↑)
< 200 (↓)
Pituitrin
administration
Patient feels better; No
change
in
decrease in serum serum or urine
osmolality;
osmolality
increase in urine
osmolality
Patient feels ill; no
change in serum
osmolality;
increase in urine
osmolality
285 – 320 (N to ↑)
< 200 (↓)
Treatment
• Etiologic
• Pathogenetic
- Hypothalamic DI
- Adiurecrin powder nasal spray0,03 g 1 – 3 times a day
- Adiuretin in drops 1 – 3 times a day
- Synthetic lysine vasopressin, desmopressin 1 to 2 sprays three
or four times a day.
- Pituitrin 0,5 – 1 ml subcutaneous 2 – 3 times a day.
- Nephrogenic DI
- chlorpropamide 100 to 500 mg/day
- Tegretol (400 mg/day)
- diuretics (thiazide diuretic (50 to 100 mg/day of
hydrochlorothiazide) is added to enhance the sodium depletion
and impair the ability of the tubules to generate a dilute urine)
THE SYNDROME OF INAPPROPRIATE
SECRETION OF ADH
is characterized by persistent ADH secretion
and the excretion of a concentrated urine
despite serum hypoosmolality.
Treatment
1.
2.
3.
4.
Identification of the underlying cause and measures to correct
it are important therapeutic goals.
The mainstay of therapy for the syndrome of inappropriate
ADH secretion is water restriction to less than 1 L/day.
Weight loss and an increase in serum sodium concentration
will occur 3 to 7 days after therapy has been started.
In patients who present with marked hyponatremia (less than
110 meq/L) and neurologic symptoms, particularly seizures,
infusion of 250 ml of hypertonic saline (3 % NaCI) over 2 to 4
h is indicated.
Furosemide in combination with intravenous or oral sodium
chloride sometimes is effective. The therapeutic goal is to
increase free water clearance and at the same time to
replace the sodium urinary losses .
OBESITY
is a state of increased body weight, specifically
fat, of sufficient magnitude to exert adverse
effects on health
(Obesity is characterized by excessive
accumulation of body fat)
Etiology
The cause of obesity is simple –
consuming more calories than are
expended as energy.
Why patients become obese?
Why persons consume more calories than
they expend?
Epidemiology
• Nearly 30 % of world population suffers
from different stages of obesity
• Its importance lies in the many, often
serious, complications to which obese
people are subject. In these complications
that warrant undertaking a treatment that
is so often unsuccessful
Predisposing factors
•
•
•
•
Sex
Endocrine factors. (Certain diseases of
endocrine glands are associated with obesity
i.e. hypothyroidism, Cushing’s disease,
hypogonadism.)
Psychological factor
Brain (especially, hypothalamic injury)
Body weight regulation
•
•
•
•
Enzymes, metabolic defects of peripheral receptors
Imbalance on the hypothalamus level
Endocrine system disorders
Defects of sympathetic regulation
Classification by Egorov
1. Alimentary
2. Endocrine
3. Cerebral (hypothalamic)
Classification due to deposition
of fat tissue
• upper type (abdominal, android);
• lower type (gluteofemoralis, gynoid).
Abdominal obesity
• Waist/hip ration
- >1,0 in men
- > 0.85 in women
• Waist circumference
- >102 cm in men
- > 82 cm in women
• Both methods identify those with
increased CVD risk
Classification due to
stages of obesity
A. Brock’s index
(N: weight = height – 100)
I. Weight excess < 30 %.
II. Weight excess 30 – 50 %.
III. Weight excess 50 – 100 %.
IV. Weight excess > 100 %.
B. Kettle’s index
BMI (body mass index)
(N: weight, kg / height, m2)
Overweight: 25,1 – 29,9
I. 30,0 – 34,9
II. 35,0 – 39,9
III. > 40,0
Weight (kg)
Body
mass
index
prominent
obesity
obesity
overweight
normal
low weight
Body weight regulation
Treatment
The prognosis for obesity is poor, particularly for obese
children, and the course tends to progress throughout
the life.
Obesity is a chronic condition resistant to treatment
and prone to relapse.
Most obese persons will not participate in outpatient
treatment, and those who do will not lose a significant
amount of weight.
Most of those who do lose weight will regain it.
These results are poor, not because of failure to
implement any therapy of known effectiveness, but
because no simple or generally effective therapy
exists.
The basis of weight reduction in all treatment
regimens is to establish a caloric deficit by
reducing intake below output
The simplest way to reduce caloric
intake is with a low-calorie diet.
Optimal long-term effects are
achieved with a balanced diet
containing readily available foods.
For most people, the best reducing
diet consists of their usual foods in
amounts limited with the aid of
standard tables of food values.
Such a diet gives the best chance of
long-term maintenance of the
weight loss, although it is the most
difficult diet to follow during weight
reduction
Diet
Diet.
• Many people turn to novel or even bizarre diets, of
which there are many.
• The effectiveness of these diets, if any, results, in
large part, from monotony - nearly everyone will tire of
almost any food if that is all they get to eat.
Consequently, when they stop the diet and return to
their usual fare, the incentives to overeat are
increased.
• Fasting has had considerable vogue as a treatment for
obesity, but it is now rarely used. Most patients
promptly regain most of the weight they lose. Since
fasting is not without complications, it should be
carried out in a hospital.
Several recommendations
Patient has to:
1. eat 4 – 5 times a day, only in a direct time, not
to eat between basic meal receptions;
2. eat only one portion;
3. limit a free liquid to 1,0 – 1,2 l/day;
4. not to eat with the aim of decreasing
depression, not to eat “for a company”;
5. the total daily energy intake should be between
1600 – 800 Kcal.
Physical activity
most important for maintance of weight loss
Physical activity has to be:
1) Regular (30 – 45 – 60 min walking/day 7 days/week)
2) Bring only positive emotions
3) Group support
4) Any exercise is better than no exercise (bike, walk,
dance)
Pharmacotherapy
have to be combined with diet and lifestyle changes
• Drugs that have weight loss as “side effect” –
metformine
• Many preparations (amphetamines,
phenterminefenfluramine, others) are used as
anorectic drugs. But, weight is regained after
drug treatment. Side effects: raises BP and pulse,
pulmonary HTS
• Orlistate (Xenical) (Investigation EXPERT) decreases
fat absorption and inhibits pancreatic lipase.
Side effects: oily stool, flatulence, vitamine A,D,E,K
malabsorption
Pharmacotherapy
We have to use medications in patients with
endocrine and cerebral pathology:
anti-inflammatory drugs (to treat encephalitis,
arachnoiditis)
bromcreptin, peritol (to treat hypothalamic and
pituitary disorders) and others.
Physiotherapy
Massage, automassage, circulating
shower-massage are very effective in the
treatment of the patients.
Surgery
Radical surgical
treatment may offer
some hope to
persons with morbid
obesity (100 %
overweight) in whom
all others treatments
have failed
References.
1. The Merck Manual of Diagnosis and
Therapy (fourteenth Edition)/ Robert
Berkow and others. – published by
Merck Sharp & Donhme Research
Laboratories, 1982. – P. 987 – 996.
2. Endocrinology (A Logical Approach for
Clinicians (Second Edition)). William
Jubiz.-New York: WC Graw-Hill Book,
1985. - P.34-38,52-63.