Prevention of diseases of Prevention of diseases of the endocrine system. the endocrine system.

Diabetes mellitus. Diabetes mellitus. Endemic goiter. Endemic goiter. Thyrotoxicosis.Thyrotoxicosis.

Sakharova Inna Ye., MD, Sakharova Inna Ye., MD, PhDPhD

HHypothalamusypothalamus

• consists of very small clusters of cells that are consists of very small clusters of cells that are located just above the pituitary glandlocated just above the pituitary gland

• It controls the function of the pituitary gland, It controls the function of the pituitary gland, by producing hormones that induce the by producing hormones that induce the pituitary gland, which in turn affects hormone pituitary gland, which in turn affects hormone secretion of the other glandssecretion of the other glands

• Hormones secreted by hypothalamus include Hormones secreted by hypothalamus include growth hormone-releasing hormone (GHRH), growth hormone-releasing hormone (GHRH), somatostatin and dopamine. somatostatin and dopamine.

Epiphysis (Pineal body)Epiphysis (Pineal body)

• Produce Produce melatoninmelatonin

• HypofunctionHypofunction: : insomnia, increased insomnia, increased anxiety, immune suppression, anxiety, immune suppression, decreased decreased basal body temperature and an elevated basal body temperature and an elevated level oflevel of estrogen/progesterone ratio.estrogen/progesterone ratio.

• HyperfunctionHyperfunction: : hypotensionhypotension, , inadequate inadequate function of the adrenal and thyroid glands, function of the adrenal and thyroid glands, decreaseddecreased estrogen/progesterone ratio, estrogen/progesterone ratio, Seasonal Affective Disorder (SAD). Seasonal Affective Disorder (SAD).

Hypophysis (Pituitary Hypophysis (Pituitary gland)gland)

• ““Master gland” of the organismMaster gland” of the organism

• Produce endorphinsProduce endorphins

ENDOCRINE ENDOCRINE GLANDGLAND

HORMONESHORMONES FUNCTIONSFUNCTIONS

PITUITARYPITUITARY

•ANTERIOANTERIORR

TSHTSH •Thyroid to release Thyroid to release hormoneshormones

LOBELOBE ACTHACTH •Adrenal cortex to Adrenal cortex to release hormonesrelease hormones

FSH,LHFSH,LH •Growth, maturation Growth, maturation & function of sex & function of sex organsorgans

GH/GH/

SOMATOTROPISOMATOTROPINN

•Growth of body Growth of body tissues & bonestissues & bones

PROLACTIN/PROLACTIN/

LTHLTH

•Development of Development of mammary glands & mammary glands & lactationlactation

ENDOCRINE ENDOCRINE GLANDGLAND

HORMONEHORMONE FUNCTIONFUNCTION

PITUITARYPITUITARY

•POSTERIOPOSTERIORR

LOBELOBE

ADHADH •Regulates water Regulates water metabolismmetabolism

OXYTOCINOXYTOCIN •Stimulate uterine Stimulate uterine contractions contractions

•release of milkrelease of milk

• INTERME- INTERME-

DIATE DIATE LOBELOBE

MSHMSH •Affects skin Affects skin pigmentationpigmentation

Hypofunction (Hypopituitarism):

• Head injuriesHead injuries• Brain tumorBrain tumor• Brain surgeryBrain surgery• Radiation treatmentRadiation treatment• Autoimmune inflammation (hypophysitis)Autoimmune inflammation (hypophysitis)• StrokeStroke• Infections of the brain, such as meningitisInfections of the brain, such as meningitis• TuberculosisTuberculosis• Infiltrative diseases, such as sarcoidosiInfiltrative diseases, such as sarcoidosi, , histiocytosis Xand histiocytosis Xand

hemochromatosishemochromatosis• Severe loss of blood during childbirth, which may cause Severe loss of blood during childbirth, which may cause

damage to the front part of the pituitary gland (Sheehan damage to the front part of the pituitary gland (Sheehan syndrome, or postpartum hypopituitarism)syndrome, or postpartum hypopituitarism)

• Genetic mutations resulting in impaired pituitary hormone Genetic mutations resulting in impaired pituitary hormone production production

Symptoms of hypopituitarism:Symptoms of hypopituitarism:

• Growth hormone deficiency:

- Congenital – dwarfism, nanismshort stature (height more than 2 standard

deviations below the mean for age and gender), muscle hypotonia, delayed motor development, “childs’ face”, high voice, hypogonadism, normal mental development

- Aquired – growth retardation, memory problems, hypogonadism, decresed of muscles strength

• FSH and LH deficiency:FSH and LH deficiency:Deficiency of luteinizing hormone (LH) and follicle-Deficiency of luteinizing hormone (LH) and follicle-

stimulating hormone (FSH), together referred to as stimulating hormone (FSH), together referred to as the the gonadotropinsgonadotropins, leads to different symptoms in , leads to different symptoms in men and women. Women experience men and women. Women experience oligooligo-- or or amenorrheaamenorrhea (infrequent/light or absent (infrequent/light or absent menstrualmenstrual periodsperiods respectively) and respectively) and infertilityinfertility. Men lose facial, . Men lose facial, scrotal and trunk hair, as well as suffering decreased scrotal and trunk hair, as well as suffering decreased muscle mass and muscle mass and anemiaanemia. Both sexes may . Both sexes may experience a decrease in experience a decrease in libidolibido and loss of and loss of sexualsexual functionfunction, and have an increased risk of , and have an increased risk of osteoporosisosteoporosis (bone fragility). Lack of LH/FSH in children is (bone fragility). Lack of LH/FSH in children is associated with delayed puberty.associated with delayed puberty.

- TSH deficiency:

- Congenital hypothyroidism, cretinism increased birth weight, edemas,

prolonged jaundice, low voice, enlarged tongue

- ADH (vasopressin) deficiency:

- Diabetes insipidus excessive thirst, polyuria,

hypostenuria, normal level of glucose in blood, high sodium level

Hyperfunction (Hypopituitarism):

•Excessive production of growth hormone:

Childhood: gigantismChildhood: gigantism

Adults: acromegalyAdults: acromegaly

Diagnostics:Diagnostics:

• Level of hormones in bloodLevel of hormones in blood

• X-ray of sella turcicaX-ray of sella turcica

• X-ray of hands (bone age)X-ray of hands (bone age)

• MRIMRI

• CT scanCT scan

ENDOCRINE ENDOCRINE GLANDGLAND

HORMONEHORMONE FUNCTIONFUNCTION

THYROIDTHYROID T3 & T4’T3 & T4’ •Regulate metabolic rateRegulate metabolic rate

•P,C,F metabolismP,C,F metabolism

•Regulate physical & Regulate physical & mental growth & mental growth & developmentdevelopment

THYRO-THYRO-

CALCITONINCALCITONIN

•Decrease serum Ca by Decrease serum Ca by increasing bone depositionincreasing bone deposition

PARA-PARA-

THYROIDTHYROID

PTHPTH •Increase serum calcium Increase serum calcium by promoting bone by promoting bone decalcificationdecalcification

•Hypofunction:Hypofunction:• Endemic goiter, Aquired Endemic goiter, Aquired

hypothyroidism, autoimmune hypothyroidism, autoimmune thyroiditisthyroiditis

•Hyperfunction:Hyperfunction:• Graves’ diseaseGraves’ disease

Classification of Goiter by GradesClassification of Goiter by Grades ClassificationClassification DescriptionDescription

Grade 0Grade 0 No palpable or visible goiter.No palpable or visible goiter.

Grade 1Grade 1 Mass in the neck that is consistent with Mass in the neck that is consistent with an enlarged thyroid that is palpable but an enlarged thyroid that is palpable but not visible when the neck is in the not visible when the neck is in the normal position. Moves upward in the normal position. Moves upward in the neck as the patient swallows. Nodular neck as the patient swallows. Nodular alterations can occur even when the alterations can occur even when the thyroid is not enlarged.thyroid is not enlarged.

Grade 2Grade 2 Swelling in the neck that is visible when Swelling in the neck that is visible when the neck is in a normal position and is the neck is in a normal position and is consistent with an enlarged thyroid consistent with an enlarged thyroid when the neck is palpated.when the neck is palpated.

From WHO/UNICEFFrom WHO/UNICEF

Grave’s Grave’s ophthalmopathyophthalmopathy

• Grefe symptomGrefe symptom ( (uncoveringuncovering sclera during sclera during patient is looking down)patient is looking down)

• Koher symptomKoher symptom ( (uncoveringuncovering sclera during sclera during patient is looking up)patient is looking up)

• Rosenbah symptomRosenbah symptom (lids tremor) (lids tremor)

Diffuse toxic goiterDiffuse toxic goiter (Graves disease) (Graves disease)

Lab. findings :

– levels of T3 and T4

– Serum TSH, measured by the sensitive methods, is undetectable or subnormal

• Simple goiterSimple goiter (the convertible terms are (the convertible terms are colloid goiter, adolescent goiter, juvenile colloid goiter, adolescent goiter, juvenile goiter, nontoxic goitergoiter, nontoxic goiter) is an acquired ) is an acquired enlargement of the thyroid gland with normal enlargement of the thyroid gland with normal function that is not caused by an inflammatory function that is not caused by an inflammatory process or a tumor. process or a tumor.

Lab. findings:Lab. findings:– N levels of T– N levels of T33, T, T44

– N level of – N level of thyroid-stimulating hormone thyroid-stimulating hormone (TSH)(TSH) – negative thyroid antibodies – negative thyroid antibodies

Endemic goiterEndemic goiter occurs predominantly in occurs predominantly in iodine-deficient areas. iodine-deficient areas.

Test for diagnosing iodine deficiency:Test for diagnosing iodine deficiency: Extreme deficiency occurs when daily urine Extreme deficiency occurs when daily urine

contains less then 25 contains less then 25 g of iodine; moderate g of iodine; moderate deficiency occurs when it is 25-50 deficiency occurs when it is 25-50 g and an g and an adequate intake is reflected by an excretion adequate intake is reflected by an excretion of 100-200 of 100-200 g/day.g/day.

Lab. findings in early stages and small iodine Lab. findings in early stages and small iodine deficiency:deficiency:– N or – N or slightly slightly levels of T levels of T33, T, T44

– N or – N or slightly slightly level of level of thyroid-stimulating thyroid-stimulating hormone hormone (TSH), (TSH), but these patients are but these patients are clinically euthyroid.clinically euthyroid.

Recommended daily Intake of iodine

Adults 150 micrograms/day

Children 90-120 micrograms/day

Pregnant Women200 micrograms/day

Diagnostics:Diagnostics:• LabsLabs

– Serum TSH Serum TSH (0.4 – 6.15 (0.4 – 6.15 μμU/mL)U/mL)– Serum Free T4Serum Free T4 (0.9 – 1.7 ng/dL)(0.9 – 1.7 ng/dL)– Serum T3 Serum T3 (T3 70 – 220 ng/dL)(T3 70 – 220 ng/dL)– Serum T4 Serum T4 (4.5 – 11.5 (4.5 – 11.5 μμg/dL) g/dL) – T3 Resin uptake testT3 Resin uptake test (25%-35%)(25%-35%)– Thyroid antibodiesThyroid antibodies– Serum thyroglobin Serum thyroglobin

• Radioactive iodine uptake testRadioactive iodine uptake test• Thyroid scan, radioscan, or scintiscanThyroid scan, radioscan, or scintiscan

• USD of thyroid glandUSD of thyroid gland

ENDOCRINE ENDOCRINE GLANDGLAND

HORMONESHORMONES FUNCTIONFUNCTION

ADRENAL ADRENAL CORTEX CORTEX

ALDOSTERONEALDOSTERONE •Fluid & electrolyte balance; Fluid & electrolyte balance;

•Na reabsorption; Na reabsorption;

•K excretionK excretion

CORTISOLCORTISOL •Glycogenolysis;Glycogenolysis;

•GluconeogenesisGluconeogenesis

•Na & water reabsorptionNa & water reabsorption

•AntiinflammatoryAntiinflammatory

•Stress hormoneStress hormone

SEXSEX

HORMONESHORMONES•Slightly significantSlightly significant

ENDOCRINEENDOCRINE

GLANDGLANDHORMONEHORMONE FUNCTIONFUNCTION

ADRENAL ADRENAL MEDULLA MEDULLA

EPINEPHRINEEPINEPHRINE

NOR-NOR-

EPINEPHRINEEPINEPHRINE

•Increase heart rate & BPIncrease heart rate & BP

•Bronchodilation, Bronchodilation,

•GlycogenolysisGlycogenolysis

•Stress hormoneStress hormone

Adrenal glands hyperfunction:Adrenal glands hyperfunction:

C ushing 's syndrom e(hypercortic ism )

C onn's syndrom e(hyperaldosteronism )

C ongenital adrenalhyperplasia (C AH )

Pheochrom ocytom a

• Cushing's syndromeCushing's syndrome is a multisystem is a multisystem disorder resulting from chronic disorder resulting from chronic exposure to inappropriately elevated exposure to inappropriately elevated concentrations of free circulating concentrations of free circulating glucocorticoids.glucocorticoids.

EEtiology of Cushing's syndrometiology of Cushing's syndrome

EndogenousEndogenous ((ACTH dependent 85%ACTH dependent 85%))• Cushing's disease (pituitary)Cushing's disease (pituitary)• Ectopic ACTH syndromeEctopic ACTH syndrome (s (small cell lung mall cell lung

carcinomacarcinoma)) • Ectopic CRH syndrome Ectopic CRH syndrome ((bronchial carcinoid bronchial carcinoid

tumourstumours))ACTH independent 15%ACTH independent 15% • CommonCommon:: Adrenal adenomaAdrenal adenoma, , aadrenal carcinomadrenal carcinoma• Less commonLess common:: Micronodular hyperplasiaMicronodular hyperplasia, ,

mmacronodular hyperplasia acronodular hyperplasia • RareRare:: McCune-Albright syndromeMcCune-Albright syndrome, g, gastric astric

inhibitory polypeptideinhibitory polypeptide

Exogenous Exogenous • ACTH treatmentACTH treatment• Glucocorticoid treatmentGlucocorticoid treatmentPseudo-Cushing's syndromePseudo-Cushing's syndrome • Major depressive disorderMajor depressive disorder• Alcoholism Alcoholism • Obesity Obesity

Clinical features of Cushing's Clinical features of Cushing's syndromesyndrome

• 90% - Central 90% - Central (truncal)(truncal) obesity. obesity. Fat Fat deposits may appear in the cheeks (moon deposits may appear in the cheeks (moon facies), in the dorsocervical area (buffalo facies), in the dorsocervical area (buffalo hump), and the supraclavicular areahump), and the supraclavicular area

• 85% - Hypertension85% - Hypertension• 65% - P65% - Presence of multiple purple striae resence of multiple purple striae

with a diameter >1 cm on the abdomen with a diameter >1 cm on the abdomen or proximal extremities or proximal extremities

• 60% - 60% - Muscle wasting and weakness Muscle wasting and weakness affect the proximal muscles of leg and affect the proximal muscles of leg and shoulder girdleshoulder girdle

• 40% - 40% - Easy bruising of the skin Easy bruising of the skin • 40% - Osteoporosis40% - Osteoporosis

• HyperpigmentationHyperpigmentation (palmar creases and (palmar creases and pressure points) in a patient with Cushing's pressure points) in a patient with Cushing's syndrome strongly suggests an syndrome strongly suggests an ACTH causeACTH cause ((Cushing's Cushing's diseasedisease))

• Patients may have mild hirsutism and acne, Patients may have mild hirsutism and acne, but severe but severe hirsutismhirsutism and especially and especially virilisationvirilisation strongly suggest an strongly suggest an adrenal carcinoma. adrenal carcinoma.

• Depression, lethargy, and insomnia often Depression, lethargy, and insomnia often occur at the same time as other symptoms.occur at the same time as other symptoms.

In children the dominant clinical features are In children the dominant clinical features are cessation of linear growth and weight gain; the cessation of linear growth and weight gain; the clinical course is more aggressive than in clinical course is more aggressive than in adults.adults.

• Conn's syndromeConn's syndrome is a disease of the is a disease of the adrenal glands involving excess adrenal glands involving excess production of a hormone, called production of a hormone, called aldosterone. aldosterone.

Another name for the condition is Another name for the condition is primary hyperaldosteronism. primary hyperaldosteronism.

Primary Hyperaldosteronism Primary Hyperaldosteronism (Conn's (Conn's syndromesyndrome) )

1.1. Solitary adrenal adenomas (80-90%)Solitary adrenal adenomas (80-90%)2.2. Bilateral adrenal hyperplasia (10-20%) Bilateral adrenal hyperplasia (10-20%) 3.3. Adrenal Carcinoma (rare) Adrenal Carcinoma (rare) 4.4. Unilateral Adrenal Hyperplasia (very Unilateral Adrenal Hyperplasia (very

rare) rare)

Clinical features of CClinical features of Connonn's 's syndromesyndrome

• Often Often aasymptomatic symptomatic • Frontal Frontal hheadache eadache • Muscle Muscle wweakness eakness to flaccid paralysis to flaccid paralysis

decreased muscle strength (decreased muscle strength (because because of of low potassium levellow potassium level))

• Polyuria and Polydipsia (carbohydrate Polyuria and Polydipsia (carbohydrate intolerance) intolerance)

• HypertensionHypertension

Hypofunction of adrenal glandsHypofunction of adrenal glands

Addison's d isease(prim ery adrenal insuffic iency)

The causes of Addison's The causes of Addison's disease include: disease include:

• Actual destruction of the adrenal glands Actual destruction of the adrenal glands through cancer, infection, or other diseases. through cancer, infection, or other diseases.

• Use of corticosteroids as a treatment causes Use of corticosteroids as a treatment causes a slow down in production of natural a slow down in production of natural corticosteroids by the adrenal glands. corticosteroids by the adrenal glands.

• Certain drugs used to treat fungal infections Certain drugs used to treat fungal infections may block production of corticosteroids in may block production of corticosteroids in the adrenal glands. the adrenal glands.

• Usually, the cause is unknown. Usually, the cause is unknown.

SymptomsSymptoms::• WeaknessWeakness, , FatigueFatigue, , Dizziness Dizziness • Arterial hypotensionArterial hypotension• Dark skin Dark skin • Black freckles Black freckles • Bluish-black discoloration Bluish-black discoloration

around the nipples, mouth, around the nipples, mouth, rectum, scrotum, or vagina rectum, scrotum, or vagina

• Lack of appetite Lack of appetite • Weight loss Weight loss • Muscle aches Muscle aches • NauseaNausea, , VomitingVomiting, , Diarrhoea Diarrhoea • Intolerance to cold Intolerance to cold • Dehydration Dehydration

Diagnostics of adrenal glands Diagnostics of adrenal glands disorders:disorders:

• Hormons level in blood and urineHormons level in blood and urine• Products of hormons’ metabolism in Products of hormons’ metabolism in

blood (blood (hydroxyprogesteronhydroxyprogesteron))• Products of hormons’ metabolism in Products of hormons’ metabolism in

urine urine (17-ketosteroids(17-ketosteroids))• Hormons supression testsHormons supression tests• Biochemical blood testing (pH, Biochemical blood testing (pH,

electrolytes)electrolytes)• Molecular geneticsMolecular genetics• MRI, CT scan, USD of adrenal glands MRI, CT scan, USD of adrenal glands

QUESTIONSQUESTIONS

??