PITUITARY DISEASES Dr.Fakhir yousif

Hyperprolactinemia Prolactinoma Acromegaly Craniopharyngioma Diabetes insipidus

Causes of hyperprolactinemia Common Present with hypogonadism and/or galactorrhea Drug induced dopamine antagonist antipsychotic, antidepressant, antiemitics dopamine -depleting reserpine, methyldopa Estrogens(occp) Causes of hyperprolactinemia physiological stress pregnancy lactation nipple stimulation sleep coitus exercise baby crying

Pathological -prolactinoma -primary hypothyroidism -polycystic ovary common -prolactinoma -primary hypothyroidism -polycystic ovary -macroprolactinemia uncommon -hypothalamic dis -renal failure -pit tumor secreting prolactin & GH Rare -chest wall reflex (herpes zoster) - ectopic source

Clinical assessment In women *galactorrhea (lactation in the absence of breast feeding) * hypogonadism : secondary hypogonadism, anovulation, infertility In men * decrease libido * reduce shaving *lethargy *rarly galactorrhea if associated with gyenicomastia Other features of hypopituit, local complication and hormone excess

Investigations -upper limit 500mU/L Exclude pregnancy Measure serum prolactin -upper limit 500mU/L -500-1000mU/L in non pregnant and lactating indicate stress and drugs, repeat test -1000-5000mU/L either due to drugs, microprolactinoma or dissconnection ->5000mU/L highly suggestive of macroprolactinoma Test for gonadal functions (testosterone, LH, FSH) TSH & T4 (to exclud primary hypothyroidism) MRI or CT scan if prolactin >1000mU/L Test for hypopituitarism

Management Correct underlying cause(cessation of drug, thyroxin replacment for prim hypothyroidism) Dopamine agonist (bromocriptin, cabergoline, quinagolide) Treat prolactinoma

. Dopamine agonist therapy: drugs used to treat prolactinomas Disadvantages Advantages Oral dose*   Ergotamine-like side-effects (nausea, headache, postural hypotension, constipation) Frequent dosing so poor compliance Available for parenteral use Short half-life; useful in treating infertility 2.5-15 mg/day 8-12-hourly Bromocriptine Rare reports of fibrotic reactions in various tissues Proven long-term efficacy Limited data on safety in pregnancy Associated with cardiac valvular fibrosis in Parkinson's disease Long-acting, so missed doses less important Reported to have fewer ergotamine-like side-effects 250-1000 μg/week 2 doses/week Cabergoline Untested in pregnancy A non-ergot with few side-effects in patients intolerant of the above 50-150 μg/day Once daily Quinagolide

1-PROLACTINOMA In premaenopausal women - mostly microadenoma, and present as hyperprolactinemia. In men and postmenopausal women – almost macroadenomas and present insidiously with mass effect. Occasionally can secrete excess GH and cause acromegaly. There is relation between prolactin conc and tumor size. Investigated like other pit tumors.

Management Medical Dopamin agonist drugs (reduce s prolactine and cause tumor shrinkage), can be withdrawn after few years in some patients with microadenoma. In macroadenomas only withdraw drugs after curative surgery or radiotherapy and under supervision. Bromocriptin and cabergoline (ergot derived) associated with fibrosis reaction in heart causing tricusped regurgitation

Surgery and radiotherapy - only for macroadenomas that fail to shrunk with dopamine agonists - if patients intolerant for dopamine agonists - trans-sphenoidal surgery for microadenomas with 80% cure rate ( lower rate for macroadenoma) - radiotherapy for some macroadenoma to stop dopamine agonists

To achieve pregnancy - dopamine agonist may be followed by pregnancy - if microadenoma withdraw dopamine agonist if get pregnant - if macroadenoma continue dopamine agonist during pregnancy with follow up for visual field and prolactin

2-ACROMEGALY Clinical features GH SCREATION FROM PITUITARY TUMOR USUALLY MACROADENOMA Clinical features Before puberty –gigantism In adults—acromegaly In adolescent and persist ---combined Headache and sweating are most common complaint. Other features of hypopituitarism

Investigations Measure GH during oral GTT---in acromegaly failure to suppress GH with paradoxical rise in 50% Prolactine elevated in 30% Other pit function tests In diabetics difficult to diagnose by GTT -measure IGF-1 *if only DM, IGF-1 is low *if DM with acromegaly, IGF-1 is high Colonoscopy to screen for colonic cancer f

Management 1.Surgical Trans-sphinoidal surgery as first line and to debulk the tumor Second line therapy with radiotherapy or medical according to post operative imaging and GTT results 2.Radiotherapy Second line if acromegaly persist after surgery Risk of hypopituitarism

Somatostatines can be used as first line as alternative to surgery 3. Medical therapy -second line treatment following surgery may be stopped years following radiotherapy -somatostatines analogues octeriotides and lanreotide as slow release injections every few wks Somatostatines can be used as first line as alternative to surgery Dopamine agonists are less potent GH receptor antagonist pegvisomant as daily self injection for some patientsnot responding to somatostatin

3-CRANIOPHARYNGIOMA Benign tumors develop in cell rest of Rathke’s pouch Located in sella tursica or commonly in suprasellar space Cystic with solid component that may be calcified More common than adenomas in young Present as pressure symptoms, hypopituitarism or cranial DI. Also features of hypothalamic damage Treated surgically by craniotomy Radiotherapy usually needed Often recur, causing morbidity of obesity, visual failure and water balance problems

Dr.Arwa M Fuzi Alsarrf 13- 3- 2012

4-DIABETES INSIPIDUS Uncommon. Persistent excretion of excessive quantities of dilute urine and thirst. Types 1. cranial DI (deficient ADH secretion by hypothalamus 2. nephrogenic DI (renal tubules are not responding to ADH) Dr.Arwa M Fuzi Alsarrf

Causes of diabetes insipidus Cranial Structural hypothalamic or high stalk lesion Idiopathic Genetic (dominant and recessive). Nephrogenic Genetic Metabolic (hypokalemia, hypocalcaemia) Drugs (lithium, demeclocycline) Poisoning (heavy metals) Chronic kidney disease (polycystic kidney ,sickle cell, infiltrative dis.

Clinical features Investigations Polyuria and polydipsia (5-20 L /day urine of low specific gravity and osmolality Potentially lethal condition if unconscious pt or hypothalamic damage Differntial d is primary polydipsia Investigations low serum ADH Urine <600 mOsm /kg + increase plasma osmolality >300mOsm/kg Water depreviation test 5% hypertonic saline infusion to inc plasma osmolality then measure ADH Pituitary function test and imaging

No coffee, tea or smoking on the test day water deprivation test ( To establish a diagnosis of diabetes insipidus, and differentiate cranial from nephrogenic causes) protocol No coffee, tea or smoking on the test day Free fluids until 0730 hrs on the morning of the test, but discourage patients from 'stocking up' with extra fluid in anticipation of fluid deprivation No fluids from 0730 hrs Attend at 0830 hrs for body weight, plasma and urine osmolality Record body weight, urine volume, urine and plasma osmolality and thirst score on a visual analogue scale every 2 hrs for up to 8 hrs Stop the test if the patient loses 3% of body weight If plasma osmolality reaches > 300 mOsm/kg and urine osmolality < 600 mOsm/kg, then administer DDAVP 2 μg IM 100 Protocol Body_ID: TI020047.150

Interpretation of water deprivation test Diabetes insipidus is confirmed by a plasma osmolality > 300 mOsm/kg with a urine osmolality < 600 mOsm/kg Cranial diabetes insipidus is confirmed if urine osmolality rises by at least 50% after DDAVP Nephrogenic diabetes insipidus is confirmed if DDAVP does not concentrate the urine Primary polydipsia is suggested by low plasma osmolality at the start of the test Interpretation Body_ID: TI020047.250

Management For cranial DI DDAVP (des-amino-des- aspartate-arginine vasopressin/ desmopressin. Long half life analogue of ADH Administered intranasally ,(5 ug morning and 10 ug evening). given IM in sick pts Adjust the dose according to s. level of Na&/or osmolality Excessive treatment cause water intoxication & hyponatremia For nephrogenic DI treated by thiazide diuretics and NSAID