Hyperprolactinaemia. Introduction.  Prolactine (PRL) is secreted from the Anterior Hypophisis.  Normal blood level of PRL: IU/L or 12.5 – 25 ng/ml. or 12.5 – 25 ng/ml.  During pregnancy,  a tenfold increase in serum PRL level.

 There are at least 4 basic molecular types of PRL hormone circulating in the normal women’s blood : ~Little Prolactin (native PRL), MW 23 kDa. ~Big Prolactin, MW ± 50 kDa. ~Big-big Prolactin, MW ± 150 kDa. ~Glycosilated Prolactin, MW 25 kDa.

Definition.  Hyperprolactinaemia is inapropriately increased PRL level occuring when the woman is non-pregnant, and may cause amenorrhoea or galactorrhoea or both.

Aetiology  Pituitary(Hypophisis) tumor; 1.Microadenoma :<10mm diameter 1.Microadenoma :<10mm diameter 2.Macroadenoma:>10mm diameter. 2.Macroadenoma:>10mm diameter.  Hypothyroidism. Primary hypothyroidism  TRH    PRL production. Primary hypothyroidism  TRH    PRL production.  Drugs : Dopamine agonist: Dopamine agonist: Phenothiazines,Butyrephenones, Phenothiazines,Butyrephenones, Benzamides,Cimetidine,Methyldopa Benzamides,Cimetidine,Methyldopa Other drugs: antidepressants,opiates,cocaine etc Other drugs: antidepressants,opiates,cocaine etc  Idiopathic

Diagnosis  The diagnosis of hyperprolactinaemia can be made on a single serum measurement.  A serum PRL of ≥800 IU/L in the presence of oligo-or amenorrhoea,  pathological significance.  CT-scanning or MRI should be done to exclude a hypophysis tumor.

Mechanism of amenorrhoea.  Raised PRL  Disturbance of normal hypothalamic GnRH release  LHpulsatility suppressed  Anovulation/Amenorrhoea.  Control of PRL release: 1.  TRH  Hypothalamus  hypophysis  PRL 1.  TRH  Hypothalamus  hypophysis  PRL 2.  Dopamine  hypophysis  PRL 2.  Dopamine  hypophysis  PRL 3.  Estrogen  hypophysis  PRL 3.  Estrogen  hypophysis  PRL 4. Breast suckling  TRH….  PRL 4. Breast suckling  TRH….  PRL

Treatment. 1. Medicament. a. Bromocriptine;2,5mg orally 2-3 X daily with meals.Or by vaginal administration. a. Bromocriptine;2,5mg orally 2-3 X daily with meals.Or by vaginal administration. b. Quinagolide.(A new dopamine agonist),once a day,tolerated better. b. Quinagolide.(A new dopamine agonist),once a day,tolerated better. c. Cabergoline ( a new dopamine agonist, long half-life.Administered weekly. c. Cabergoline ( a new dopamine agonist, long half-life.Administered weekly.

2. Surgical treatment. * Trans-sphenoidal surgery is usually done to resect both micro-and or macroadenomas. * Trans-sphenoidal surgery is usually done to resect both micro-and or macroadenomas. * The results of treatment vary greatly between centres,±50% * The results of treatment vary greatly between centres,±50% 3. Radiotherapy (very rare)

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Pituitary Adenoma  Pituitary adenomas secreting hormones other than prolactin may also affect menstrual function. * ACTH secreting tumor  cortisol  Cushing’s disease. * ACTH secreting tumor  cortisol  Cushing’s disease. * Adenoma or adenocarcinoma of the adrenal cortex may  cortisol. * Adenoma or adenocarcinoma of the adrenal cortex may  cortisol. * Ectopic production of ACTH by other tumors such as Bronchial carcinoma or carcinoid tumors * Ectopic production of ACTH by other tumors such as Bronchial carcinoma or carcinoid tumors  cortisol.  cortisol.

CUSHING’S SYNDROME  Cortisol excess  protein catabolism   gluconeogenesis  conversion to fat  deposition to face,neck and trunk.  Cortisol excess  depression of immune reaction.  Cortisol excess  protein catabolism  wasting of limbs. wasting of limbs.  Excess of other steroids: Estrogen  amenorrhoea Estrogen  amenorrhoea Androgen  mild virilism Androgen  mild virilism

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HYPERANDROGENEMIA  Hyperandrogenemia is a condition that the circulating level of testosterone, dehydro- testosterone and adrostenedion, is high, and may stimulate the derangement of physical condition.  Normal Androgen level: depends on the phase of the menstrual cycle.  Increase LH level   androgen.

CLINICAL APPEARANCES  PCOS is  Functional derangaement of the Hypothalamo-pituitary-ovarian axis associated with anovulation.  LH levels relatively high,FSH  LH levels relatively high,FSH levels are relatively low. levels are relatively low.  LH:FSH ratio elevated.  LH:FSH ratio elevated.  LH  levels of Testosterone,Androstene  LH  levels of Testosterone,Androstene dione and DHA from Ovarium dione and DHA from Ovarium

 Some of these androgens  estrone in peripheral tissues  High androgen levels   SHBG by 50%  unbound,active androgens  The pathophysiology of PCOS is unknown (Genetic element?) (Genetic element?)

Clinical features of PCOS  Variable  The classic ‘Stein Leventhal’ syndrome,: * oligomenorrhea * oligomenorrhea * hirsutism * hirsutism * obesity * obesity * infertility. * infertility.

Diagnosis of PCOS  No specific features of PCOS are diagnostic of the condition.  on clinical grounds supported by : 1.Ultrasound  *follicular cysts(Ø:6-8mm) 1.Ultrasound  *follicular cysts(Ø:6-8mm) *  ovarian volume *  ovarian volume ( 25% of normal women) ( 25% of normal women)  Eleveted LH:FSH ratio.  Eleveted free testosterone levels.

2. Infertility  ovulation disorders. 3. Amenorrhea, 4. Obesity 5. Hirsutism

Long- term effects of PCOS  Increased risk of endometrial cancer(3X)  Increased risk of Diabetes Mellitus (Hyperinsulinemia due to insuline resistance)  Increased risk of hypertension and cardiovascular disease.

Treatment of PCOS  Aimed at relieving symptoms and preventing long term effects.: * Infertility  :1. Treat cause if known eg.  PRL. * Infertility  :1. Treat cause if known eg.  PRL. 2. Ovulation induction. 2. Ovulation induction. * Amenorrhea  :1. need contraception  * Amenorrhea  :1. need contraception  combined OC Pills combined OC Pills 2. need no contraception 2. need no contraception  cyclical gestogens  cyclical gestogens

* Hirsutism  1.Local treatment * Hirsutism  1.Local treatment 2.Medicament treatment.: 2.Medicament treatment.: * Low dose oral contraceptivwes * Low dose oral contraceptivwes * Medroxyprogesterone acetate * Medroxyprogesterone acetate * Cyproterone acetate * Cyproterone acetate * Dexamethasone * Dexamethasone * GnRH analoque (addback HRT) * GnRH analoque (addback HRT) * Etc. * Etc.

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