Endocrine__pituitary gland by abdialasso

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									   In Capsule Series
Endocrine


                           Pituitary gland

            Present in cella tursica.
            Weight 0.5 gm.
            Connected to i hypothalamus by i pituitary stalk.
            Divided into :
              - ant. lobe → vascular connection.
              - post. lobe → neural connection.
            Histology of ant. lobe :
              - Chromophobe : non functioning → ( reserve).
              - Chromophil :
                  • acidophil : G.H. & prolactin.
                  • basophile : ACTH, TSH, FSH, LH & MSH.
            Regulation : hypothalamus secrete :
              - releasing       &
              - release inhibiting factor for each hormone.
            Function of hormones :
              - G.H.        :
                          •   CHO : hyperglycemia.
                          •   fat : lipolysis.
                          •   protein : anabolic (bone, muscle & viscera)
                          •   minerals : ↑ all i minerals ( Na, K, Ca & PO4).
              - Prolactin     :
                        •     milk secretion.
              - FSH           :
                        •     ♀      → maturation of graffian follicle.
                        •     ♂      → spermatogenesis.
              - LH            :
                        •     ♀      → ovulation.
                        •     ♂      → testosterone formation by i testis.
              - ACTH                 :
                        •     secretion of suprarenal hormones :
                                 o cortisone +++
                                 o androgen ++
                                 o aldosterone +
              - TSH           :
                          •   secretion of T3 & T4 by thyroid gland.
              - MSH           :
                          •   skin pigmentation.


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                         Acromegaly
  1. Physiology :
       a. Hormone       :                 G.H.
       b. Gland    :         Pituitary gland.
       c. Function of the hormone         :
                i.   CHO        :       hyperglycemia.
               ii.   fat        :       lipolysis.
              iii.   protein    : anabolic (bone, muscle & viscera).
             iv.     minerals   : ↑ all i minerals ( Na, K, Ca & PO4).
       d. Regulation of this hormone :
               i. ↑ G.H. :
                     1. GHRF.         (growth hormone releasing factor)
                     2. hypoglycemia.
                     3. sleep.
              ii. ↓ G.H. :
                     1.    GHRIF. (growth hormone release inhibiting factor)
                     2. hyperglycemia.
                     3. stress    &     exercise.
  2. Etiology :
       a. Adenoma.
       b. Hyperplasia.
       c. Exogenous intake.
  3. C / P :
       a. C / p of i cause :
               i. Adenoma     →    ↑ ICT.
              ii. Homonyms hemianopia.
       b. C / p of i hormone :
               i. CHO           :     D.M. in 30% of cases.
              ii. Fat           :     excess lipolysis
                                            → loss of s.c fat
                                            → wrinkling of i skin
                                            → hyperlipidemia.
             iii. Protein       :     excess growth of         - bone,
                                                               - muscles
                                                               - viscera.

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               1.  bone
                     a. face         :     Ape like
                           i. enlarged nose, ears, lips & tongue.
                          ii. bone :       big skull,
                                prominent : - supra-orbital ridges
                                     &       - mastoid processes.
                         iii. prognathism        :     prominent
                                lower jaw é separated teeth.
                        iv. hypertrophy of larynx é hollow deep
                              voice.
                     b. hands & feet:
                           i. spade hands & enlargement of feet.
                          ii. frequent change in rings & shoes.
                        iii. Osteoarthritis.
               2. visceromegaly :
                     a. hepatosplenomegaly.
                     b. cardiomegaly.
               3. muscle power :
                     a. ↑↑ early.
                     b. ↓↓ late.
         iv. Minerals :
                      Na. retention        →     HTN.
      N.B. :     HTN is due to :
                          • Endothelial hyperplasia.
                          • Na retention.
         v. Associated endocrinal manifestation :
               1. hyperprolactinaemia in 30% of cases.
               2. DM in 30% of cases.
         vi. Others  :
               1. neurological manifestations :
                    a. depression.
                    b. peripheral neuritis due to :
                         i. interstitial neuropathy.
                        ii. carpal tunnel syndrome.
                       iii. diabetic neuropathy.
               2. pressure manifestations :
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                                   pituitary tumor →    visual defects
                                        ( bi-temporal hemianopia. )



  4. Investigation :
       a. Inv. for i cause :
                  i. Imaging for i gland :
                       1.      X-ray on skull.
                       2.      C.T. & M.R.I. for skull.
       b. Assay of i hormone level :
                  i. In blood :
                       1.      ↑ G.H. [ normal < 5 n.gm/ml.]
                       2.      ↑ insulin growth factor ( IGF-1) → ↑↑ in
                               acromegaly.
                       3.      ↑ prolactin in 1/3 of cases.
    N.B. :
             GH is difficult to measure because of its pulsatile secretions
             So , insulin growth factor ( IGF-1 ) produced by liver in
             response to GH is measured instead.
       c. Inv. of i function of i hormone :
                  i. Blood :
                        1.     ↑ glucose.
                        2.     ↑ free fatty acids.
                        3.     ↑ Ca.     &     ↑ P.
                 ii. X-ray :
                        1.     skull :
                                 a. thickening of cortex.
                                 b. prognathism.
                       2.      hand :
                                     mushroom shape.
       d. Suppression test :
                                  material :          glucose I.V.
                       1.      normal                 →    ↓ G.H. level.
                       2.      in acromegaly          →    no change.

  5. Treatment :
       a. Surgery : hypophysectomy
       b. Irradiation.

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                  c. Antagonism :
                           i. Somatostatine analogue [GHRIF] : octereotide.

                  d. Symptomatic ttt : of
                            i. D.M.
                           ii. Hypertension.

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                                        Gigantism
       Def. :        ↑↑ GH secretion before fusion of epiphysis.

       C/P :
                  1. Generalized overgrowth of skeleton & soft tissue.
                  2. Later on features of acromegaly develops.
                  3. Lastly decline stage usually occurs ( pituitary hypofunction.)


                Differential diagnosis of tall stature
       Causes :
          1. Familial & racial : [ i commonest ]
          2. Gigantism.

          3. Excess androgen          → tall children , short adult
          4. Cerebral gigantism
          5. Marfan’s syndrome.

          6. Klinefelter syndrome (47 xxxy)




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               Hypopituitarism in adults
                (Pan hpypopituitarism)

  1. Physiology :
          Refer to acromegaly.

  2. Etiology :
       a. Destruction of pituitary gland by :
                 i. Surgery               → in ttt of Hyperfunction.
                ii. Irradiation           → in ttt of Hyperfunction.
               iii. Tuberculosis, sarcoidosis, heamochromatosis.
       b. Sheehan’s syndrome :
               pituitary infarction after sever post-partum hge ?
       c. Neoplasm          :     acidophil adenoma.
       d. Trauma            :     fracture base of i skull.
       e. Idiopathic        :     auto-immune.

  3. C / P :
       a. C / p of i cause :
                 i. Surgery.
                ii. Irradiation.
               iii. Sever post-partum bleeding.
       b. C / p of i hormone :
          According to i frequency of appearance, i following occur :
                 Gondotrophines & GH (2g) are lost early
                      then → TSH         then → ACTH deficiency.
               i. Gonadal deficiency :
                     1. ♀ : amenorrhea, loss of libido, infertility, loss of
                         pubic & axillary hair.
                     2. ♂ : impotence, loss of libido, infertility, loss of
                         pubic & axillary hair.
              ii. GH deficiency :
                            No clinical manifestations in adult
                     1. skin wrinkling & weakness.
                     2. ↑↑ sensitivity to insulin ( hypoglycemia ).
             iii. TSH deficiency :
                         result in hypothyroidism.

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             iv. ACTH deficiency :
                          Results in 2ry adrenal insufficiency it
                          simulates Addison’s disease except :
                   1. no pigmentation              → absent ACTH.
                   2. no marked hypotension due to presence of
                       aldosterone.
          N.B. :
                aldosterone production is mainly dependant on i
                renin- angiotensin system not on ACTH.
              v. Coma :
                            Causes of coma :
                     1. hypoglycemic coma due to GH & cortisone.
                     2. myxoedema coma.
                     3. pressure in cases of pituitary tumors.
          N.B. :
                   If i patient has associated DI & hyperprolactinaemia
                   the problem is at i hypothalamus.

  4. Differential diagnosis :
       a. From 1ry hypognadism :               → high FSH.
       b. From 1ry Addison’s disease :
                i. skin pigmentation.
               ii. high ACTH.
              iii. marked hypotension.
       c. From anorexia nervosa :
                i.   normal hair & breast.
               ii.   aggressive attitude.
              iii.   normal cortisol.
             iv.     high G.H. due to hypoglycemia.
       d. From thyroid myxoedema : see later
  5. Investigation :
       a. Inv. for i cause :
               i. Imaging for i gland :
                    1. X-ray : shows i sella tursica.
                    2. C.T. & M.R.I.          → i best.
       b. Assay of i hormone level :
                       1.   ↓ G.H. [ normal = 1 – 5 n.gm/ml.] & ↓ IGF-1.
                       2.   ↓ FSH, ↓ LH &        ↓ sex hormones.
                       3.   ↓ TSH,    ↓ T3 &     ↓ T4.
                       4.   ↓ ACTH         &     ↓ cortisol.
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      c. Inv. of i function of i hormone :
                   1.   hypoglycemia.
                   2.   hyponatremia.
      d. Stimulatory test :
               stimulatory test →        for Hypofunction.
                          material       :     insulin.
                          I.V. insulin followed by TRH & GnRH.
                   1. normal →           ↓ blood sugar    → marked
                       elevation of GH, TSH, FSH, LH & cortisol.
                   2. in pan-hypopituitarism : no change.

  6. Treatment :
      a. TTT of i cause.
      b. Replacement therapy :
             i. Hydrocortisone :        dose : 30 mg/ day.
                                        20 mg a.m. & 10 mg p.m.
              ii. Gonadal hor.s :       ♂ → testosterone.
                                        ♀ → estrogen/progesterone.
             iii. Thyroxin       :      dose 0.1 – 0.2 mg/day.
                                 given after steroid replacement.
            iv. Recently         :
                     1. purified pituitary hor.s.
                     2. hypothalamic releasing factors.




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       Differential diagnosis of short stature

Causes :
  1.          : familial & constitutional : the commonest
  2. Endocrinal
         a.   ↓ GH : Levi-lorian, Frolich’s, Laurance Moon Biedle.
         b.   ↓ T4 :      cretinism &         juvenile myxoedema.
         c.   ↑ sex hormones :          precocious puberty.
         d.   ↑ cortisol :      Cushing       or    excess steroid ttt.
  3. Chronic sever illness during childhood               :
         a. CVS           :      sever rheumatic fever,
                                 congenital heart diseases.
         b. Lung          :      polycystic lung disease.
         c. GIT           :      mal-absorption &       malnutrition.
         d. Kidney        :      chronic nephritis.
  4. Skeletal causes :
         a. Congenital         :
                i. Aconrdoplasia :          short limbs é normal trunk.
               ii. Osteochondrodystrophy           :
                         both limbs & trunk are short & deformed.
         b. Acquired :
                i. Rickets.
               ii. Pott’s disease of spine.
              iii. Paget’s disease of bone.
  5. Genetic causes              :
         a. Mongolism [Down’s syndrome] trisomy 21.
         b. Turner’s syndrome [ 45+ XO ].
         c. Noonan’s syndrome




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                Hyperprolactinaemia
  1. Physiology :
       a. Hormone :              Prolactin.
       b. Gland :         Pituitary gland [anterior lobe].
       c. Function of the hormone :
                i. Necessary for lactation.
               ii. ↓↓ GnRH.
       d. Regulation of this hormone :
                i. ↑ prolactin :
                              PRH ( prolactin releasing hormone.)?
                       Recently it’s thought that TRH ( thyrotropin
                       releasing hormone ) is a prolactin releasing hor.
               ii. ↓ prolactin :
                              PRIH ( prolactin release inhibiting hor.)
                                          → dopamine.

  2. Etiology :
       a. Physiological : pregnancy ,            lactation ,       stress,
                                 sleep       &   nipple stimulation.
       b. Drugs :
                i. Dopamine antagonist :  phenothiazines.
               ii. Dopamine depletors : methyl-dopa & reserpine.
       c. Diseases of many organs :
                  i. Pituitary :
                        1. tumors :         prolactinoma.
                        2. diseases : grnuloma & sarcoidosis.
                 ii. Thyroid : 1ry hypothyroidism →↑ TRH→ ↑ prolactin.
                iii. Renal :     CRF → ↓ prolactin clearance.
               iv. Liver cirrhosis : → ↓ metabolism.
  3. C / P :
       a. C / p of i cause :
                 i. Tumor.
                ii. Dopamine antagonist.
               iii. Liver cirrhosis or CRF.
       b. C / p of i hormone :
                i. ♀ :
                         1.   glactorrhea.
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                     2.   amenorrhea.
                     3.   osteoprosis (due to estrogen deficiency).
              ii. ♂ :
                     1.   impotence.
                     2.   loss of libido.
                     3.   infertility.
                     4.   gynaecomastia.
                     5.   never glactorrhea.

  4. Investigation :
       a. Inv. for i cause :
               i. Imaging for i gland :
                     1. U/S.
                     2. C.T. & M.R.I.
              ii. Liver & renal function tests.
       b. Assay of i hormone level :
                       Prolactin > 300 n.gm/ml     → suggestive of
                             [ n < 20 ng / ml ].   pituitary adenoma.
       c. Inv. of i function of i hormone :
                i. Glactorrhea.
               ii. Infertility.
              iii. Pressure manifestations.

  5. Treatment :
       a. Dopamine agonist :
                i. Bromocriptine : dose 1.25 mg at bed time
                            ↑ gradually to 15 mg/day.
               ii. Cabergoline : drug of choice →less side effects.
       b. Surgery:          trans-sphenoidal              or
                            trans-cranial     →    removal of i tumor.
       c. Irradiation :     proton      or     particles.
       d. TTT of i cause : e.g. :       myxoedema.




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                        Diabetes insipidus
  1. Physiology :
       a. Hormone : ADH (antidiuretic hormone)[ vasopressin ].
       b. Gland :         Pituitary gland [ posterior lobe ].
       c. Function of the hormone :
                  i. ↑↑ water reabsorption by renal tubules.
                 ii. Large dose     →     v.c. of bl. vessels.
       N.B. :
             ADH is synthesized in hypothalamus & then transported
          along axons & stored in i post. Pituitary.
       d. Regulation of this hormone :
                  i. ↑↑ ADH by :
                        1. ↑ osmolarity.
                        2. hypovolemia.
                        3. stress
                        4. drugs :
                             a. nicotine.
                             b. barbiturates.
                 ii. ↓↓ ADH by :
                        1. ↓ osmolarity.
                        2. hypertension.
                        3. cold weather.

  2. Etiology :
       a. Central DI → damage of hypothalmo-hypophyseal axis:
                   Idiopathic
                   i.              :     starts in childhood.
                   Tumor.
                  ii.
                   Trauma : head injuries & after hypophysectomy.
                 iii.
                iv.Granulomas : T.B.            &      sarcoidosis.
       b. Familial DI ( Walfram syndrome) [ DIDMOAD ] hereditary
          condition →        defect in osmo-receptrs ass. é
                i. DI        diabetes insipidus.
               ii. DM        diabetes mellitus
              iii. OA        optic atrophy
             iv. D           deafness.
       c. Nephrogenic DI ( Renal tubules not responding to ADH )
                  i. Hereditary .

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               ii. Acquired        :   2ry to          :
                     1. renal tubular acidosis.
                     2. kidney amyloidosis.
                     3. hypercalcemia.
                     4. hypokalemia.
                     5. drugs :
                          a. lithium.
                          b. cholchicine.
  3. C / P :
       a. C / p of i cause :
                i. Surgery     →    hypophysectomy.
               ii. Tumor       →    ↑ intracranial tension.
       b. C / p of i hormone :
                  i. Polyuria & nocturia   :      5 – 20 L/day.
                 ii. Dehydration ,                polydepsia,
                     weight loss           &      low grade fever.
                iii. Hypovitamonosis       :      of water soluble vitamins.
               iv. Complications           :      shock.

  4. Differential diagnosis :
          Other causes of polyuria.   [discussed later].
                    especially ; psychogenic polydepsia.
          N.B. :
               DI      :
                             - polyuria      →    polydepsia.
                             - so ; there is ↑↑ osmolarity.
               Psychogenic polydepsia :
                             - polydepsia →       polyuria   .
                             - so ; there is ↓↓ osmolarity.

  5. Investigation :
       a. Inv. for i cause :
                i. Imaging for i gland :
                     1. X-ray.
                     2. C.T.        &    M.R.I.
       b. Assay of i hormone level :
                i. In blood.
               ii. In urine.
       c. Inv. of i function of i hormone :

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              i. Urine analysis :
                    1. Polyuria é no pathological constitutes.
                    2. Specific gravity :          low.
                    3. After fluid deprivation : - polyuria persists.
                                       &           - Sp.G. fails to rise.
             ii. Plasma osmolarity :                             ‫ا‬       ‫ا‬
                        ↑↑ due to loss of free water é high plasma Na.
      d. Tests for localization of i cause :
               i. Test i hypothalamus :
                               material            :    nicotine.
                       smoking cigarette or inject 1-3 ml nicotine.
                     1. normal :            oliguria.
                     2. in case of central DI :         no change.
              ii. Test osmo-receptrs :
                               material : I.V. hypertonic saline
                                            ( NaCl 2.5 % ) .
                     1. normal :            oliguria.
                     2. if i lesion is in osmo-receptrs ( e.g. familial DI ) :
                                            no change.
             iii. Test kidney :     [ to ( ) central DI & nephrogenic DI ]
                               material :          vasopressin.   [ test ‫] أه‬
                     1. in central DI              :    oliguria.
                     2. in nephrogenic DI :             no change.

  6. Treatment :
      a. TTT of i cause.
      b. Diet :      excess fluid, salts, fats, CHO & vitamins.
      c. Replacement therapy :
                     Desmopressine ( synthetic ADH )
                         nasal spray ; twice daily.
      d. Drugs :
                     Cholropropamide & Carbemazepine ( tegretol )
                     may be used in nephrogenic DI both sensitize
                     renal tubules to ADH.




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                                SIADH
Syndrome of inappropriate anti-diuretic hormone
                  It means an excessive release of ADH

   1. Physiology :
                     Refer to diabetes insipidus.
   2. Etiology :
         a.   Tumor    → oat cell carcinoma.
         b.   Pulmonary lesion :Legionella pneumonia , T.B.
         c.   CNS      :     meningitis, encephalitis & head injuries.
         d.   Drugs    :
                   cholropropamide,carbamazepine,cyclophosphamide
   3. C / P :
                • Increased ADH causes water retention      → water
                  intoxication  →  dilutional hyponatremia ( nausea,
                        vomiting, confusion, headache, convulsions &
                        coma.)
                • No edema because of natriuresis.
   4. Investigation :
                        1. ↓ Na (< 130m.Eq /L )
                        2. ↓ serum osmolarity(< 270m.osmol/L.) & ↑urine
                           osmolarity ( > 300 m.osmol/L.)
N.B. :        Normal renal , adrenal & thyroid functions.
   5. Treatment :
         a. Fluid restriction → 800-1000 ml / day.
         b. demeclocycline:
                  i. 600-1200 mg /day → inhibit i action of ADH.
                 ii. Given to patient unresponsive to fluid restriction.
         c. For sever hyponatremia : hypertonic saline 1.8% slowly é
            fursemide to treat hyponatremia.




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      Differential diagnosis of polyuria
  1. Physiological      :
                    winter months.
                    excess coffee or tea.
                    Diuretics.
  2. Psychological :
         Hysterical polydepsia.
         Differs from D.I. : → fluid deprivation → normal.
                             → no improvement after ADH.
  3. Pathological       :
      a. Endocrinal            :
               i.   D.I.
              ii.   D.M.
             iii.   Adrenal :       Conn’s , Cushing’s , Addison’s.
            iv.     Thyroid         : thyrotoxicosis.
             v.     Parathyroid     : hyperparathyroidism.
      b. Renal                 :
               i.   Nephrogenic DI         : end organ unresponsiveness.
              ii.   Acute renal failure →       diuretic phase.
             iii.   Chronic renal failure.
            iv.     Fanconi syndrome
      c. Miscellaneous :
                After attacks of
                migraine, epilepsy, bronchial asthma            &
                paroxysmal tachycardia.




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