Download Hypophysial nanism

Lecture No 9.
HYPOTHALAMO-HYPOPHYSIAL SYSTEM.
IT'S PARTICIPATION IN CORRECTION OF
ENDOCRINE GLANDS FUNCTIONAL
ACTIVITY.
DISORDERS OF HYPOTHALAMOHYPOPHYSIAL SYSTEM.
Prepared of prof. L.Bobyreva
Hypophysis
is a small endocrine gland,
located in the Turkish
saddle (sella turcica) of the
basilar bone. The weight is
approximately 0.7 g, and
the size is 10х12х5 mm.
1 – capsule, 2 – adenohypophysis,
3 – follicle of intermediate part,
4 - neurohypophysis
HYPOPHYSIS
Intermediate lobe
Anterior lobe
basophile
cells
ACTH, TSH,
FSH, ICSH, ТТH
eosinophilic
cells
SТГ,
prolactin
Posterior lobe
chromophobes
cells
melanotropin
ADH
(vasopressin),
oxytocin
Histologically there are three groups of
cells in the anterior lobe of the
hypophysis:

basophile cells compose 4-10% of the cell
structure of adenohypophysis, which are subdivided
into 3 subtypes of cells, secreting ACTH, TSH,
follicle-stimulating hormone (FSH), and
luteinizing (interstitial cell-stimulating)
hormone (ICSH);


eosinophilic cells compose 30-50% of the cell
structure and are subdivided into 2 subtypes of
cells secreting somatotropic hormone and
prolactin;
chromophobes don't participate in the hormone
formation. They are the source of eosino- and
basophiles.


Intermediate lobe of hypophysis secreting
melano-stimulating hormone: some authors
think that is a part of anterior lobe or
adenohypophysis.
Posterior lobe of hypophysis (neurohypophysis)
serves as a reservoir for neurohormones storage.
The neurohormones (vasopressin and oxytocin)
pass to the posterior lobe through cell axons, which
are located in hypothalamic nuclei, where their
synthesis takes place. Neurohypophysis is the place
of depositing and peculiar activation of
neurohormones passing here, after that they are
released into the blood.
Pituitary hormones
 somatotropic
hormone (STH)
– stimulates the synthesis of protein in the bones, liver and other
inner organs;
– influences transient lipogenetic action (within 30-40 min) on the
lipid exchange, then it increases the lipolysis processes;
– has the short-term insulin-like action (within 30-40 min) on the
carbohydrate metabolism, then the gluconeogenesis activates in
the liver;
– stimulates the function of α-cells, increases the glucagons content,
which activates enzymes destroying insulin. It leads gradually to
the absolute insulin insufficiency and diabetes mellitus
development;
– under the influence of STH, the tissue structures of the organism
grows including connective tissue, the muscles and inner organs
(heart, lungs, and liver). The mechanism of this action consists of
the formation and releasing of somatomedins, insulin-like factor of
growth I and II, which are the messengers of anabolic and growth
influence of STH;
– the level of STH in the blood serum is 0.3-3.9 mkg/l (0.33.9 ng/ml).
Pituitary hormones



Prolactin is gonadotropic hormone, as it stimulates the
function of yellow body. But the major physiological effect
of the prolactin is the stimulation of mammary glands'
secretion;
ACTH (adrenocorticotropic hormone) stimulates the
synthesis of glucocorticoids through the adrenal cortex and
it stimulates the synthesis of mineralocorticoids partially.
The level of ACTH in the blood is 10-150 ng/l
(10-150 pg/ml);
TSH (thyrotrophic hormone) stimulates the
biosynthesis of thyroid hormones (T3, T4), their flow into
the blood, assists the hyperplastic processes in glandular
tissue of the thyroid gland. The level of TSH in the blood is
0.5-1.5 mkg/l (0.5-1.5 ng/ml);
Pituitary hormones


FSH (follicle-stimulating hormone) is gonadotropic
hormone (it stimulates the activity of sexual
glands(gonads). In women it activates the growth of
ovarian follicles. Its level in the blood is 6-14 ME/l in the
stage of proliferation, 14-20 ME/l in the stage of ovulation,
and 4-9 ME/l in the stage of secretion. In men it activates
the growth of testicular tubules, its level in the blood is
5-25 ME/l (5-25 mME/ml);
ICSH (luteinizing (interstitial cell-stimulating)
hormone) is gonadotropic hormone (it stimulates the
activity of gonads). In women it assists in the ovulation and
development of yellow body in ovaries. Its level in the
blood is 10-18 ME/l in the stage of proliferation, 40-70 ME/l
in the stage of ovulation, and 8-12 ME/l in the stage of
secretion. In men it activates the growth and function of
interstitial cells (Leydig's cells) in testicles, its level in the
blood is 5-25 ME/l (5-25 mME/ml). The level in the blood is
5-25 ME/l (5-25 mME/ml);
Pituitary hormones



ADH (antidiuretic hormone, vasopressin) and
oxytocin are produced in the supraoptical and the
paraventricular nuclei of hypothalamus and pass along
stalk to the neurohypophysis, where they are
accumulated in the Geryng's bodies.
ADH increases the water reabsorption in distal portions
of adrenal tubules, that leads to the decreasing of
diuresis;
Oxytocin stimulates the uterus contractions and
increases the lactation.
nuclei of
hypothalamus
nuclei of
hypothalamus
neurohypophysis
adenohypophysis
melanotropin
TSH
STH
ACTH FSH
Skin
lactation hormone
luteotrophin
ProgesSteroEstro-terone
Testoides
gen
sterone
Hypothalamus and hypophysis
are the common correlated
system of the organism. The
relation of hypothalamus and
hypophysis realizes by the
means of neurosecretory tracts
of feedback system or "plusminus interactivity". It
provides the normal hormone
production in the organism and
due it the constancy of internal
environment and various
functions of the organism are
supported. The regulation of
hormone secretion of
adenohypothysis is realized by
the release factors or
releasing hormones, which
are present for all tropic
hormones of hypophysis.
Disorders of Hypophysis
WITH THE DECREASING
OF THE FUNCTION
WITH THE INCREASING
OF THE FUNCTION
DIABETES INSIPIDUS
PARHONE'S SYNDROME
HYPOPITUITARISM
(SYMMONDS' DISEASE)
ITZENKO-CUSHING'S
DISEASE
HYPOPHYSIAL NANISM
ACROMEGALIA AND GIANTISM
ACROMEGALIA


Acromegalia is the disease connected with
excessive secretion of STH.
Etiology:
in 90% of all cases of acromegalia it is related with the
adenoma of hypophysis (more often with eosinophilic, rare
with combined or chromophobe), which is benign adenoma
as a rule. In other cases the acromegalia development is
related with various disorders of hypothalamus, which lead
to the excessive production of growth hormone-releasing
factor (that in turn leads to hyperplasia or excessive
secretion of STH) and somatostatin formation may be not
excessive. Sometimes the somatoststin secretion stops and
can lead to removal of inhibitory effects of somatoststin
concerning to eosinophilic cells of adenohypophysis. As the
result the relative increasing of growth hormone-releasing
factor and hyperproducing of STH occur.
ACROMEGALIA

The clinical picture
– the disease occurs at the age of 30-50 years, more often
in women and very seldom in children;
– the clinical signs of the disease develops slowly;
– general weakness, fatigue, headache as a rule in the
frontotemporal region, in the region of superciliary arches,
bridge of nose and eyeball, which are connected with
adenoma hypophysis pressure on diaphragm of Turkish
saddle by the tension of pachymeninx and with the
increasing of intracranial pressure;
– the change of appearance is noticed: the enlargement of
the nose, ears, hands, and feet;
– the rontgenography of the skeleton shows the typical
signs:
 osteoporosis;
 prognathism and teeth separation;
 increasing of paracranial sinuses;
 thickness of calvarium;
 increasing of sizes of Turkish saddle.
ACROMEGALIA
А
Б
А – patient with acromegalia,
Б – health.
Patient with acromegalia
Healht
Health
Patient with acromegalia
ACROMEGALIA

The clinical picture
– splanchnomegalia – essential part of the clinical
picture;
– frequent arterial hypertension;
– hyperglycemia and glycosuria (diabetes mellitus);
– in female – disturbance of menstrual cycle, down to
amenorrhea;
– in male – decrease of sexual potency, libido,
spermatogenesis and atrophy of testicles;
– according to tumor grows and it overrunning beyond
turkish saddle signs of squeezing by tumor
oliencephalon parts and cranial nerves function
disturbances appears;
– compression of optic chiasm bring to development of
bitemporal hemianopsia, congestive optic papilles,
decrease of visual acuity, down to amaurosis.
ACROMEGALIA

DIAGNOSTICS:
– increase of STH level in blood serum up
to 20 ng/ml (norm 3.0–4.0 ng/ml);
– craniography (changing of Turkish saddle,
signs of increased intracranial pressure);
– congestive disks of optic nerve, changes
of vision fields and visual acuity;
– hyperglycemia and glycosuria.
ACROMEGALIA

The treatment
– surgical treatment: hypophysectomy;
– roentgenotherapy: γ-therapy of hypothalamo-hypophysial region
or protontherapy (form three regions – two temporal and one
frontal regions). The total dose is 2.000-4.000 rads. The single
dose is 75-90 rads. In the case of progressive tumour, the course
of roentgenotherapy is repeated in 6-8 months. The γ-therapy in
the form of radioactive cobalt (Со60): the total dose is 4.0005.000 rad. Protonotherapy: nongraded stereotactic irradiation of
the hypophysis ina dose of 4.000-9.000 rads;
– parlodel (bromcryptin): for first 2 or 3 days it is administered in
a dose of 2.6 mg (1 tablet), when the side effects are absent the
dose can be increased to 10-20 mg a day;
– dehydrative and hypotensive therapy (aminophylline, magnesium
sulphate);
– symptomatic therapy of disease complications (diabetes mellitus,
toxic goitre, hypothyroidism).
Itzenko-Cushing's disease


Itzenko-Cushing's disease is a disease, which is
manifested by the bilateral hyperplasia of adrenal
glands, increased secretion of ACTH, and hormones
of adrenal cortex.
First, the disease was described by the Russian
neuropathologist N.M.Itzenko in 1924. In 1932
the same symptom was described by the American
neurosurgeon Cushing.
Etiology:
- craniocerebral injury;
- neuroinfection;
- hormonal remodulation in the period of
menopause, pregnancy and others.
Itzenko-Cushing's disease

Pathogenesis
Under the influence of excessive production of
corticoliberin (its secretion is stimulated by serotoninand acetylcholinergic neurons), the hyperplasia of
adenohypophysis cells producing ACTH occurs. During
long-term production of corticoliberin, this hyperplasia
gradually developing changes into microadenoma and
then into adenoma with the ability for autonomic
production of ACTH. This leads to the bilateral
hyperplasia of adrenal cortex, the increasing of
synthesis and secretion of corticosteroids, which cause
the symptomatic of Itzenko-Cushing's disease,
influencing on the metabolism.
Itzenko-Cushing's disease
THE CLINICAL PICTURE
Disease occurs in women in 4-5 times more often than in men. It
develops at the age of 25-45 years.
 obesity (lipopexia is present in the region of shoulder girdle,
abdomen, supraclavicular spaces, mammary glands, and spine.
The face has crescent-shaped, round form, the cheeks are red.
This typical kind of the face is called "matronism". The obesity
is typical in 95% of patients);
 rose-purple strips, related with disorder of protein
metabolism, are located on the skin of the abdomen, axillary
region, shoulder girdle, thighs, and buttocks;


excessive pilosis, hirsutism;
arterial hypertension, moderate as a rule, and sometimes
220-225/130-145 mm Hg (the natrium retention leads to
increasing volume of circulatory blood);
Itzenko-Cushing's disease
THE CLINICAL PICTURE



disturbance of the menstrual cycle is manifested by
opso-, oligo-, or amenorrhea, which is typical in 70-80%
patients;
muscular weakness is related with hypokaliemia.
Sometimes it is marked very much and patients can not
stand up from the chair without help of other person;
osteoporosis and pathological fractures of the spinal
column and limbs are revealed in 90% patients. The
catabolic effect of glucocorticoids leads to the decreasing of
protein bone matrix, the amount of organic substances and
their components are decreased too, and this condition leads
to increased resorption of calcium from the bone. Parallel
with it the absorption of calcium in the intestine is decreased
and its loss with the urine is increased.
Itzenko-Cushing's disease
Itzenko-Cushing's disease
The laboratory data




polycythemia, lympho(cyto)penia,
eosinopenia, and neutrophilic leukocytosis;
potassium decreasing;
radiographic data: osteoporosis of bones;
the increasing of the level of ACTH and
corticosteroids within 24 hours (the
disturbance of their daily regimen is noted).
Itzenko-Cushing's disease
The treatment:





parlodel (bromcriptine) in a dose of 2,5-7,0 mg a day;
radiotherapy is administered according to separate intensive
method by increasing doses: 75-100-150-200-250 rads beginning
every second day, then daily, so as to the patient must receive
900-1.000 rads a week (the course dose is 4.500-5.000 rads). The
most stable remission is attained by the repeated course of
radiotherapy in 7-9 months. The satisfactory results are observed
in 50-60% patients;
hypophysectomy;
unilateral or bilateral adrenalectomy (it is performed in two
stages: after removal of the second adrenal gland, cortisol in a
dose of 250-300 mg is administered; then (within 8-9 days) the
dose is decreased to 100 mg; after that prednisolone is
administered in a dose of 5-15 mg within 24 hours (2/3 dose is
administered in the morning and 1/3 dose in the evening);
combined therapy (unilateral adrenalectomy with the following
röntgenotherapy or drug therapy).
Itzenko-Cushing's disease
Patient Е.: А – before treatment, Б – 3 year after subtotal
adrenalectomy.
Hypophysial nanism (hypophysial
dwarfism, hypophysial microsomia,
hypophysial nanocormia)
It is a genetic disease caused by absolute
or relative deficiency of STH in the
organism. It leads to the inhibition of the
skeleton, organs and tissues. The sudden
growth inhibition is marked the age of 23
years
in
genetic
nanism.
Male dwarfish stature is below
130 cm, female dwarfish stature is
below 120 cm. The rate of the disease is
1:30.000 persons. First the disease was
described by A. Paltuff in 1891.
Hypophysial nanism
Etiology:


genetic disease, which is inherited as
autosomal-recessive sign;
organic lesions of hypothlamohypophysial region (trauma,
hemorrhage, tumours
(craniopharyngioma), meningitis,
tuberculosis and others).
Hypophysial nanism
Pathogenesis:
Together with the insufficiency of growth
hormone in hypophysial nanism, the decrease of
gonadotropic hormone producing is often noted. The
decreasing of thyrotrophic hormone occurs rarely,
and the decreasing of corticotropic hormone is noted
very rarely.
This state lead to the decreasing of the functions
of the following peripheral endocrine glands: thyroid
gland, gonads, and adrenal cortex. Their hormones
have stimulating effect on the growth.
In some cases this disease can occur in the
persons with the normal content of STH in
insensibility of the peripheral tissues to it or in the
absence of the biological activity of this hormone.
Hypophysial nanism
Pathogenesis (continuation):
The hypophyis is often hypoplazed only,
sometimes there are atrophic changes,
which are caused by abnormal process
(tumour, hemorrhage ans others) or
changes in the hupophysis and
hypothalamus are absent.
Hypoplasia and atrophy can develop in
the thyroid gland or gonads, and very
rarely in the adrenal glands. The skeleton
and inner organs have small sizes.
Hypophysial nanism
Classification:
а) the form with proportional constitution (the
person has normal body proportions):
 hypophysial nanism (Paltauff dwarfism);
 hypothyroid (myzematose) nanism;
 nanism in adrenogenital syndrome (adrenal);
 nanism occurring in a result of thymus gland
disease;
 infantile type of nanism occurring in a result of
exogenous influences (alimentary insufficiency,
toxic factors and others);
 dwarfism in early puberty with premature
closure the growth zones.
Hypophysial nanism
Classification:
b)



form with disproportionate
constitution:
rachitic nanism;
chondrodystrophic nanism;
dwarfism in congenital bones fragility.
Hypophysial nanism
The clinical picture:








proportional constitution;
the skin is pale, wrinkled, sometimes dry with yellowish
tint;
subcutaneous fatty layer develops badly, but sometimes
there is a lipopexia in the abdominal region, in the region
of mammary glands, pubis, and thighs;
the muscular system develops poor;
the formation of the skeleton remains behind the passport
age;
splanchnomicria, but their function is not disrupted;
sexual infantilism, males suffer from cryptorchidism
sometimes, females suffer from amenorrhea. The
secondary sex signs and sexual attraction are absent;
in all types of genetic nanism the intellect is retained.
Hypophysial nanism
The laboratory diagnostics:







the decreasing of the STH level;
the decreasing of the activity of alkaline
phosphatase;
the decreasing of the level of the inorganic
phosphorus;
the test of tolerance to carbohydrates (TSH) is flat;
there is a disposition to hypoglycaemia;
the level of protein-binding iodine (PBI) is on the
lowest limit of the norm or below;
the daily excretion of 17-CS, 17-OCS, and
oestrogens is decreased;
in the radiologic investigation there is a delay of
focus of bone appearance and a closure of bone
lines.
Hypophysial nanism
Patient Е., 16 year old. Height 102 sm.
Hypophysial nanism
Patient Н.,
17 year old.
Growth
zones are
open.
Hypophysial nanism
The treatment:



anabolic steroids with the aim of stimulation of the growth
and physical development (metandrostenolone in a dose of
0.1-0.15 mg/kg of body weight within a day or retabolile in
a dose of 1 mg/kg of the body weight one time a month
i/m);
somatotropin in a dose of 2-4 units i/m three times a week,
intermittent regimen: 2 months and then 2 interval months;
for stimulation of the development and functions of gonads
beginning with the age of 16 years, chorionic gonadotropin
is injected in a dose of 1.000 to 1.500 units 1-2 times a
week i/m. The course consists of 10-15 injections. It is often
combined with the injections of methyl testosterone in male,
and estrogenic preparations in female. After growth zones
closure, the treatment by the preparations of sex hormones
according to the patient's sex is administered in ordinary
therapeutic doses.
DIABETES INSIPIDUS
HYPOTHALAMIC
DIABETES INSIPIDUS
ABSOLUTE DEFICIENCY OF
ANTIDIURETIC HORMONE
RENAL (NEPHROGENIC)
DIABETES INSIPIDUS
GENETIC PATHOLOGY
OF ADH RECEPTORS, IT INHERITS
AS RECESSIVE SIGN
WHICH LINKED WITH SEX
(IN MALES)
Diabetes insipidus is a disease related with abnormality of the
synthesis, transport, and releasing of vasopressin. First, it was
described by Thomas Willis in 1674. The family form of hypothalamic
diabetes insipidus was described by Lacomb in 1841.
DIABETES INSIPIDUS

Etiology:
– neurotropic virus infections;
– acute and chronic diseases (scarlet fever, whooping cough,
sepsis, typhoid fever and relapsing fever, epidemic (louseborne) typhus, tuberculosis, syphilis);
– craniocerebral injury;
– pituitary tumour, chromophobe adenoma of hypophysis more
often;
– Simmonds' disease;
– Shihan's (Shien's) syndrome.

Pathogenesis:
– The impairment of supraoptical and paraventricular nuclei of
the hypothalamus or hypothalamo-hypophysial tract leads to
the absolute deficiency of ADH (vasopressin). Sometimes the
deficiency of ADH connected with congenital pathology of renal
tubules to ADH.
– The deficiency of ADH lead to the decreasing of water
reabsorption in the distal renal tubules. This condition causes
polyuria.
DIABETES INSIPIDUS

The clinical manifestations:
–
–
–
–

appear suddenly as a rule, and gradually rarely;
polacyuria and polyuria (daily diuresis up to 40 l);
polydipsia;
asthenoneurotic syndrome: insomnia, irritability,
degradation.
Laboratory data:
– total and biochemical analysis of blood is normal;
– the urine is colorless, transparent, with subacid reaction;
doesn't contain the sugar and other pathological
admixtures. The relative density of the urine is 1.0011.005.
DIABETES INSIPIDUS
Classification
1. Diabetes insipidus is caused by the absolute deficiency
of ADH:
a) connected with organic impairments of
hypothalamo-hypophysial endocrine complex;
b) idiopathic (spontaneous).
2. Diabetes insipidus is caused by the relative deficiency of
ADH:
a) connected with the increased activation of ADH in
the peripheral regions;
b) “renal diabetes insipidus“ (complete or significant
insensibility of the distal portion of the renal tubules
to ADH).
DIABETES INSIPIDUS
The treatment:
In the diet the excessive amount of vegetables, fruit and
milk products is used.
The goal of the treatment is the elimination of the
disease's cause (antibiotics, anti-inflammatory drugs and
others).
Hormone-replacement therapy:
ADIURECRINE (powder-like extract of the posterior
lobe of pituitary gland of cattle), intranasal introduction
in a dose of 0,03-0,05 g 2-3 times a day. The duration
of drug effect is 6-8 hours ;
PITUITRIN (water extract of the posterior lobe of
pituitary gland) is injected subcutaneously in a dose of
1 ml (5 units) 3-4 times a day. The duration of drug
effect is 4-5 hours.
DIABETES INSIPIDUS
The treatment:
–
–
–
–

MINIPRINE (DESMOPRECINE): tablets in a dose of 10200 mkg under the tongue till full resorption (1-3 tablets);
AUDIPRECINE: bottles 0.01% 2,5 ml (70 drops), 1 drop is
5 mkg of the preparation: 1-8 drops a day;
H-DESMOPRECINE-SPRAY: bottle containing 2,5 ml (25 doses)
and 5 ml (50 doses) in the form of inhalation; 10 mkg of
preparation for 1 nasal injection: 1-4 nasal injections in a day;
CHLORPROPAMIDE: 100-350 mg within 24 hours. Sugarreducing preparation of sulfanilurea, which stimulates the
releasing of ADH (vasopressin) from the posterior lobe of
pituitary gland. If there is a combination of diabetes mellitus
and diabetes insipidus. The drug doses must be increased to
500 mg a day.
THE PROGNOSIS is favorable.