PATHOLOGY OF HYPOTHALAMIC-PITUITARY

AREA

As.-prof. Svystun I. I.

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- CRH - GIH (somatostatin)- TRH - PIF (dopamine)- GnRH- GHRH

Regulation

Etiology of hypothalamo – pituitary disorders

1. Tumor (craniopharyngiomas) or metastasis

2. Infectious diseases:- acute (scarlet fever, influenza)- chronic (tuberculosis, malaria, toxoplasmosis)

3. Trauma

4. Vascular damaging (thrombosis, thromboembolia)

5. Metabolic disorders (xanthomathosis)

6. Congenital pituitary hypo – or aplasia

7. Empty sella syndrome

7. Genetic predisposition

8. Idiopathic

Manifestation of hypothalamo – pituitary disorders

• Hypersecretion (PRL, GH, ACTH)

• Hyposecretion (panhypopituitarism)

• Sellar enlargement (X-ray, CT, MRI)

• Visual loss (bitemporal hemianopsia or visual field defects)

Pituitary tumors• Slow – growing (benign)• 10 – 15 % of all brain tumors:- Prolactinomas 60%- GH-secretion 20%- ACTH excess 10%

• Clinical presentations:1. Mass effect:- Headaches- Seizures- Facial pain or numbness- Apoplexia - Nausea, vomiting

2. Visual loss (bitemporal hemianopsia or visual field defects)

3. Hormonal effects (overproduction or deficiency)

Classification of hypothalamo – pituitary disorders

• Adenohypophysis disorders1. Secretion of GH- overproduction: acromegaly, giantism- dificiency: pituitary dwarfism2. Secretion of ACTH- overproduction: Cushing’s syndrome3. Secretion of Prolactin- overproduction: hyperprolactinemia, galactorhea-amenorhea4. Secretion of TSH - thyrotoxicosis5. Secretion of Gonadotropines: adiposogenital-dystrophy6. Hypopituitarism7. Hypothalamic obesity• Neurohypophysis disorders1. Dificiency of vasopresin: diabetes insipidus2. Inapropritiative secretion of vasopresin

GROWTH-HORMONE EXCESS(acromegaly and gigantism)

Chronic disorder resulting from excessive 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

Etiology1. Adenoma (acidophilic or chromophobe) of

the pituitary2. Ectopic GH-producing tumors (cancer of

lungs, mamma glands, pancreatic gland)3. Regulatory hypothalamus disturbances

(overproduction of somatoliberin or deficiency of somatostatin)

4. Ectopic GRH-producing tumors (carcinoid tumor of intestine,lungs)

Clinical manifestations of gigantism• Mass effects• Overproduction of GH- height more than 190 cm in

women and 200 cm in men- Hypersecretion of GH prior to

closure of epiphysis leads to proportional growth of bone; both length and width of bone are increased

- May be blood hypertension, myocardiodystrophy, atrial fibrillation

• Leonid Stadnyk - 7 feet 7 inches (231.1 cm) with Yushchenko V. (president of Ukraine 2005-2010), 183 sm.

Acromegaly - Named “acromegaly” by

Pierre Marie in 1886 from Greek akron (extremities) and megas (large)

- Rare condition- 3 – 4 new cases per million

population per year- Affects both sexes equally- Peak ages 40 – 60 years- Mortality 10 times higher

than in control group mostly due to cardiovascular disorders

Clinical manifestations of acromegaly

• Syndromes connected with influence of GH on organs and tissues:

1) periostal overgrowth:- overgrowth of the

mandible leads to protrusion of the jaw (prognatism)

- there ia an overbite and the teeth become separated (diastema).

2) cortical thickening(characteristic coarsening of the facial features)

3) Hypertrophy of soft tissues of hands and feet (the hands are widened and the fingers become broad, requiring a larger ring size. Similar changes in the feet require a larger shoe size)4) arthropathy, carpal tunnel syndrome 5) Hypertrophy of tongue, sleep apnoe

6) The skin is thickened, andfemales may note hypertrichosis, excessive sweating

II. Changes from the inner organs:- Hepatomegaly and cardiomegaly- Hypertension is present in 40 % of patients - The kidney may also become enlarged, and renal clearance of

phosphate is frequently impaire

III. Syndrome of reproductive disturbances:- Amenorrhea, which occurs in as many as two-thirds of female

patients, may be the chief complaint. Decreased libido, impotention is experienced by one-third of the patients (due to prolactin – like effects of GH)

IV. Syndrome of endocrine disorder- thyromegaly is present in about 25 % of the patients (hyper-

and hypothyroidism occurs rarely) - the abnormalities in glucose metabolism (diabetes mellitus)- hyperfunction or deficiency of other pituitary trophic hormones

V. Mass effects (headaches, vision field disorders)

Diagnosis of acromegaly is usually suspected from:

1. The patient's history

2. Physical examination

3. Laboratory investigations:- The level of GH (0,5 – 5,0 ng/ml)- IGF-1- Test with glucose suppression of

growth-hormone secretion- Test with TRH

• Value of old pictures

3. Enlargement of the sella turcica (90 % of patients) X-ray, CT,MRT

4. Visual - field defects (bitemporal hemianopsia)

Differential diagnosis• Gigantism

- constitutional high height

- Klainfelter’s syndrome

- Marphan syndrome• Acromegaly

- hypothyroidism

- Peget’s syndrome

Pharmacologic therapy1. A dopaminergic agonist and ergotamine derivative, 2a-

bromergocriptine (bromocriptine 10 to 60 mg/day, (clinical remissions in 73 % patients, normalization of GH level in 22 % of patients).

Side effects include nausea, orthostatic hypotension, consti pation, 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.

3. SOMAVERT (pegvisomant for injection) is a prescription medicine for acromegaly. It is for patients whose disease has not been controlled by surgery, radiation, and/or other medical therapies, or patients for whom these options are not appropriate. The goal of treatment with SOMAVERT is to have a normal IGF-I level in the blood.

Treatment Surgery: - Transsphenoidal hypophysectomy is the procedure of

choice. Advantages: effectivity in nearly 90 % of the patients, simplicity

and low morbidity. Side effects: hypopituitarism, 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.

Epidemiology- 3 – 4 new cases per 1million

population per year

- affects both sexes equally

Etiology• Congenital deficiency of GH- Genetic disorders - Defect of pituitary gland development (aplasia, hypoplasia)

• Acquired deficiency of GH- trauma, neoplasms (craniopharyngioma), infection

• Peripheral resistance for GH- Pathology of GH receptors (Laron’s syndrome)- Biologically inactive GH

No demonstratable etiology (idiopathic hypopituitarism) (The latter is more frequent in males than in females)

Classification

A. Organic (trauma, neoplasms, infection).

B. Idiopatic (primary or secondary, due to hypothalamic deficiency).

1. Panhypopituitarism.

2. Isolated GH deficiency (may be hereditary and transmitted as an autosomal recessive trait, in other instances a hereditary basis cannot be established).

Clinical manifestations. The height of adult men is less than 130 cm,

and adult women is less than 120 cm.

1. Child is born with normal weight and height.2. Growth retardation can be observed since 3 – 4

years (the increasing of the height is not more than 1 cm per year).

3. The patient, despite small size, has normal body proportions.

4. Mental develoment is normal.5. Secondary hypothyroidism.6. Secondary adrenal insufficiency.7. Puberty will not appear because of a lack of

gonadotropic hormons (secondary hypogonadism).8. The passport age is not corresponding with biologic

age.9. In patients with isolated GH deficiency the patients

have normal pituitary function (other than lack og GH), undergo normal puberty, and have normal reproductive capacity

Jyoti Amge's, 15 y.o.,born December 16, 1993a resident of Nagpur, India

• Born Karl Kosiczky on September 21 1918 in Prakendorf, Hungary (now in Slovakia), he stopped growing at the age of four and was diagnosed with pituitary dwarfism. Karl Slover, who has died aged 93, was a member of the "Singer Midgets" vaudeville troupe and played several roles as a Munchkin in the 1939 film classic The Wizard of Oz.

Premordial dwarfism1. Child is born with decreased weight and height

(1000-1200 g); 2. Growth retardation can be observed from

earliest infancy3. Sexual development occur normally or at only a

slightly retarded rate 4. Bones abnormalities5. Mental retardation

Diagnosis

Clinical picture (carefully recorded growth charts may disclose the time of onset of the disease)

level of GH, IGF-1

X-ray examination of the skull and hands

Fields of vision

Before the diagnosis of pituitary dwarfism can be made, all other etiologies must be ruled out

Differential diagnosis – hypothyroid dwarfism

- chondrodystrophy- progeria (syndrome of Getchison -

Vilford). - Villi - Prader syndrome

- Terner syndrome - somatogenic dwarfism

- Constitutional (normal variant) short stature.

- Psychosocial dwarfism .

Treatment.I. Balanced diet.II. Complex of physical exercises.III. Pharmacotherapy.1. GH (synthetic). Indications: a low level of GH or a low level of

somatomedin in patients with biologic age less than 12 – 13 years and passport age more than 3 years. Doses of 2 – 4 IU of GH given IM at night time three times a week for 2 – 3 months with 2 – 3 months break have accelerated the rate of linear growth, through often this therapeutic effect is not sustained.

2. Anabolic steroids under the control of biologic (osteal) age.3. Thyroid replacement.4. 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.

5. Vitamin therapy.IV. 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.

Epidemiology

- affects mostly women at age 20 - 40

EtiologyPrimary:- pityitary aplasia, hypoplasia, - tumors (chromophobe adenomas, craniopharyngiomas,

pituitary cysts) - postpartum uterine hemorrhage (Sheehan's syndrome)- autoimmune and infiltrative (hemochromatosis,

sarcoidosis) processes- Infectious (tuberculosis, fungi)- pituitary irradiation or surgery- traumatic or surgical destruction of the hypothalamic-

pituitary areaSecondary:• Hypothalamic disorders

Classification

• Total or panhypopituitarism

• Partial hypopituitarism with isolated deficiency of one or two hormones

The symptoms of hypopituitarism mimic those of many diseases.

Watch for pituitary insufficiency: 1. In women who fail to lactate following pregnancy and

delivery. (Involution of breasts and sparse axillary and pubic hair would suggest the diagnosis.)

2. In females with unexplained amenorrhea, particularly if symptoms of ACTH and TSH deficiency or increased intracranial pressure are present.

3. In males with decreased libido and loss of axillary and pubic hair.

4. In patients with unexplained anemia. 5. In diabetic patients who experience a reduction in

insulin requirements.)

Clinical manifestationsClinical symptoms are

not present unless 75 % of the gland is destroyed.

1) Hypogonadism (early symptom)

2) Hypothyroidism3) Hypocorticism4) In children:

drowth retardation; in adult weakness, muscle atrophy, kachexia

5) Neuro – psychiatric changes, hypothalamic disorders (vegetative crises, termoregulation disorders)

6) Mass effects

Diagnosis 1. Physical examination 2. Laboratory findings• anemia, hypercholesterolemia, tendency to

hypoglycemia• hormonal assessment (decreased levels of pituitary

and peripheral endocrine glands)

3. Instrumental investigations• X-ray of cella turcica (the upper limits of normal for sellar

dimensions are length 17mm, depth 13mm, and width 15mm )• CT,MRI

• Cerebral angiography• Ophthalmologist (fields of vision, retina)

Differential diagnosis

• Anorrhexiaa nevrosa• Shien syndrome• Primary hypothyroidism• Shmidt syndrome (peripheral

autoimmune poliendocrine deficiency)

• Malignant tumors, tuberculosis, enterocolitis

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 obtain in pure form; (2) because of their nature and short half-life they have to be given i.v. 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. - Premenopausal females with ovarian failure should

be treated with estrogens.• Thyroid drugs (L-thyroxin)• Vitamins, 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).

Etiology. Causes of hypothalamic diabetes insipidus:1. Surgery2. Trauma 3. Tumors (craniopharyngioma) or metastatic (carcinoma of

the breast).4. Infiltration of the hypothalamus by leukemic cells,

granuloma (sarcoidosis, tuberculosis), histiocytes (Hand-Schuller-Christian disease), or infections.

5. Idiopathic.6. Familial.

Causes of nephrogenic diabetes insipidus1. Hereditary factors: X-linked transmission with predominance

in males.2. Acquired factors (Drugs: Lithium carbonate, demeclocycline.

methoxyflurane and amphotericin, renal diseases)

Clinical picture

1. The hallmark of diabetes insipidus is the excretion of large quantities of urine (usually 5 to 10 L/day, but the amount can be more). In mild forms of diabetes insipidus, polyuria may be minimal with urine volumes of 2 to 4 L/day.

2. Polydipsia (ingesting of large amounts of mostly cold water).

3. Insomnia, decreasing of appetite, dryness of skin and mucous membranes, pharyngitis, gastritis, constipation are common in patients.

4. In situations in which the patient has no access to water, is unconscious, or has an abnormality of the thirst mechanism, severe dehydration may ensue.

Diagnosis

1. The patient's history

2. Physical examination

3. Laboratory signs:- a specific gravity of urine less than 1,005 - an osmolality of less than 100 mosmol/kg- serum osmolality is increased. - level of ADH can be decreased

4. Instrumental, neurological, ophthalmoscopic examination

Psychogenic polydipsia

Hypothalamic diabetes insipidus

Nephrogenicdiabetes insipidus

History Insidious onset Abrupt onset, brain surgery, tumor present, steroid therapy

Family history, chronic hypokalemia, chronic hypercalcemia, postanesthesia

Physical examination

Normal hydration Dehydration may be present

Dehydration may be present

Laboratory:- serum osmolality;- urine osmolality

270 – 290 (↓ to N)< 200 (↓)

285 – 320 (N to ↑)< 200 (↓)

285 – 320 (N to ↑)< 200 (↓)

Adiuretin administration

Patient feels ill; no change in serum osmolality; increase in urine osmolality

Patient feels better; decrease in serum osmolality; increase in urine osmolality

No change in serum or urine osmolality

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.

Diagnostic criteria The characteristic features of the syndrome include:1. Hyponatremia.2. Serum hypoosmolality.3. Continuous urinary sodium excretion despite hyponatremia.4. Urine osmolalily usually greater than the serum osmolality.5. Absence of clinical edema.6. Reversal of the abnormalities following water restriction.7. Symptoms are usually not present unless the serum sodium

concentration falls below 120 meq/L. When this occurs, headaches, anorexia, nausea, and vomiting may ensue. With marked hyponatremia (100 to 110 meq/L), symptoms related to the central nervous system, such as confusion, disorientation, hostility, convulsions, and coma, may predominate. Arrhythmia may also occur.

Differential diagnosis

It is recommended that cardiac, hepatic, adrenal, and renal disease be ruled out before making the diagnosis of inappropriate ADH secretion.

The differential diagnosis of the syndrome of inappropriate ADH secretion is that

of dilutional hyponatremia.

Treatment1. Identification of the underlying cause and measures to correct

it are important therapeutic goals.2. 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.

3. 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.

4. 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 .

HyperprolactinemiaDifferential diagnosis of hyperprolactinemia

depends on the prolactin level

• >250 ng/ml (>5000 mU/l) is diagnostic of prolactin – secreting adenoma (exept for pregnancy)

• <250 ng/ml may be due:- Adenoma- Drugs (verapamil, cimetidine,

esrogens, opiates, reserpine, α-metyldopa; halaperidol, metoclopramide)

- Severe primary hypothyroidism- Interruption of pituitary stalk by

tumor or other infiltrative diseases

Clinical manifestations of hyperprolactinemia

• Hypogonadism in both women and men by supressing GnRH secretion and pulsutility, resulting in low levels of LH and FSH

Treatment of Hyperprolactinemia• Pharmacologic

1.Dopamine agonists are the first line treatments: bromcriptin- Inroduced in Europe in 1970’s- Stimulates D2 receptors on lactotroph inhibiting prolactin

synthesis and release- Side effects: nausea, dizziness, hypotension, nasal stuffiness

2. Other agents:

1) Pergolide 2) Carbegoline (long half life)

Treatment of Hyperprolactinemia

• Surgery cures (< 20% of large tumors

- Transphenoidal - Frontal cranitomy• Radiation therapy• Radiotherapy (gamma

knife)

Obesity

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

Health consequences• Diabetes mellitus• Hypertension• Coronary artery disease• Obstructive sleep apnea• Certain malignancies• Cholelithiasis

(gallbladder disease)• Arthritis• Infertility

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?

Predisposing factors• “Obesogenic” environment:

social,

cultural,

behavioral factors

- Excess of calorie

intake

- Sedentary

lifestyle

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)• Genetic factors (It is widely recognized that obesity

runs in families: 80 % of the offspring of 2 obese parents are obese, compared with 40 % of the children of 1 obese parent and only 10 % of the offsprings of 2 nonobese parents)

Classification by Egorov

1. Alimentary

2. Endocrine

3. Cerebral (hypothalamic)

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

Body mass index

Weig

ht (kg

)

obesity overweight normal low weightprominentobesity

Height (sm)

Limitations of BMI• Can overestimate

body fat in muscular individuals

• Can underestimate body fat in those who have lost muscles (elderly, sedimentary)

• Does not describe distribution of body fat

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

- >90 (102 )cm in men

- > 80 - 82 cm in women

• Both methods identify those with increased CVD risk

Visceral fat is metabolically active

• Cytokines:- TNF – alfa- Interleukin - 6• “Adipokines”- Resistin- Adiponectin • Prothrombotic

mediators: PAI-1

Pathogenesis: imbalance between energy supply and demand

• Insulin plays a major role in regulating of food intake• When you eat too much you will end with insulin resistance

Body weight regulation

• Enzymes, metabolic defects of peripheral receptors• Imbalance on the hypothalamus level• Endocrine system disorders• Defects of sympathetic regulation

Clinical manifestations

• Obese people come to the doctor not only complain about their fitness but also with complications:

- cardiovascular- pulmonary- orthopedic and others

Alimentary obesity

1. Genetic (family) factor.

2. Eating habits (ingestion of large amounts of food).

3. Slow progressing

Hypothalamic obesity

1. Fast gain weight (20 – 30 kg during 1 – 2 years).

2. More frequent dysplastic localization of the fat.

3. The presence of the striae.

4. Symptoms associated with increased intracranial pressure and neurologic picture (somnolence, raised appetite and others).

5. Signs of hypothalamic dysfunction (palpitation, hyperhydrosis, hypertension).

Pickwickian syndrome

It can occur in the massively obese persons.

Pressure on the thorax from the encompassing sheath of the fatty tissue combined with pressure on the diaphragm from below by large intra-abdominal accumulations may lead to reducing of the respiratory capacity, hypoventilation, retention of CO2 leading to decreased effects of CO2 as respiratory stimulant and resultant hypoxia and somnolence.

Barraquer–Simons syndrome(progressing lipodystrophia)

1. More frequent is in young women.

2. Atrophy of the subcutaneous adipose tissue in the region of face neck, thorax; increased quantity of adipose tissue in the lower part of body, thighs, legs (“riding-breeches” type).

3. Duration of the disease, as a rule, without any changes in nervous and endocrine system and patients have only cosmetic defect.

Dercum disease (generalized painful lipomatosis)

1. More frequent is in women in menopause.

2. There is localized, painful nodes (knots) in the subcutaneous adipose tissue. These nodes are painful, itch, the skin over nodes is red.

3. Patient can have normal weight or be obese.

4. Person has nervous changes (CNS asthenia, neuroses) and endocrine disturbances (decreasing of function of sexual glands).

Babinski-Fröhlich syndrome(adipose-genital dystrophy)

1. More frequently is observed in boys.

2. Characterized by obesity (dysplastic type) and hypogenitalism (development of primary and secondary sexual signs is stopped: small sizes of scrotum, penis, may be criptorchism).

3. There is often lack in growth.

Laurence-Moon-Biedl syndrome or Laurence-Moon-Biedl-

Bardet 

1. Obesity, hypogenitalism like in patients with Babinsky-Frelych’s disease.

2. Decreased mental activity or debility.

3. Pigmental retinitis.

4. Bones or inner organs abnormalities (polydactylia, syndactylia and others)

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Bardet–Biedl Syndrome

Morgagni Stewart Morel syndrome

1. More frequent in young women or in climacteric female.

2. Adipose tissue localized in the region of chin, abdomen (like apron) mammary glands (mastoptosis), skin is flabby, striae are absent.

3. Hirsutism is present (beard, moustache).

4. Hypertension.

5. Diabetes mellitus.

6. Increased thickness of lamina interna of frontal bone.

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Polycystic ovary syndrome

- Obesity - Dysmenorrhea - Infertility - Hypoplasia of uterine- Signs of virilization (beard,

moustache) - Mammary glands are served- Signs of musculanization

TreatmentThe 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

Diet

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

Several recommendationsPatient 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 activitymost 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)

Pharmacotherapyhave 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

• Meridia (sibutramine) was withdrawn from the U.S. market in October 2010.

• Orlistate (Xenical) (Investigation EXPERT) decreases fat absorption and inhibits pancreatic lipase. Side effects: oily stool, flatulence, vitamine A,D,E,K malabsorption

• Belviq (lorcaserin) affects chemicals in the brain that affect appetite (Belviq work by turning on a specific chemical “switch” in the brain that increases levels of serotonin)

• Belviq is used together with diet and exercise to treat obesity• Belviq is sometimes used to treat obesity that may be related to diabetes,

high cholesterol, or high blood pressure.• Aim-lose at least 5% of starting weight after taking the medication for 12

weeks.• People taking Belviq had an average weight loss that was 3 to 3.7

percent greater than people taking placebo.• After taking Belviq for one or two years, some 47 percent of people

without diabetes lost at least 5% of their body weight (only 23 percent of patients taking an inactive placebo lost this much weight.)

• Qsymia combines two generic drugs in a new formulation. One half the drug is composed of the seizure and migraine medication called topiramate. Topiramate causes weight loss in several ways, including increasing feelings of fullness, making foods taste less appealing, and increasing calorie burning. The other half of Qsymia is the appetite-suppressant called phentermine. Phentermine is thought to suppress appetite by triggering release of a brain chemical that increases blood concentrations of the appetite-regulating hormone leptin.

• People taking Qsymia for up to one year had an average weight loss of nearly 9 percent over those taking an inactive placebo. Over 70 percent of people taking Qsymia lost at least 5 percent of their body weight (only 20 percent of patients taking an inactive placebo lost this much weight).

Surgery Radical surgical treatment may offer some

hope to persons with morbid obesity (100 % overweight) in whom all others treatments have failed

Roux-en-Y stomach surgery for weight loss

Adjustable gastric banding