Pituitary & Hypothalamus Disorders PDF

HYPOTHALAMUS & PITUITARY DISORDERS OIA3005 PHARMACOTHERAPY OF ENDOCRINE DISORDERS LEARNING OUTCOMES  To describe the pathophysiology of pituitary and hypothalamus gland disorders  Hypothalamus dysfunction  To interpret lab results based on the  Pituitary hyposecretion...

HYPOTHALAMUS & PITUITARY DISORDERS OIA3005 PHARMACOTHERAPY OF ENDOCRINE DISORDERS LEARNING OUTCOMES  To describe the pathophysiology of pituitary and hypothalamus gland disorders  Hypothalamus dysfunction  To interpret lab results based on the  Pituitary hyposecretion principle of patient management  Panhypopituitarism  To describe the management of pituitary and  Growth hormone deficiency hypothalamus gland disorders  Pituitary hypersecretion  To solve pharmaceutical care issues that are related to pituitary and hypothalamus gland  Acromegaly disorders  Hyperprolactinemia ADDITIONAL RESOURCES  https://www.youtube.com/watch?v=YcPicFL5Jnw  https://www.youtube.com/watch?v=JlI5N2N4d-k HYPOTHALAMUS & PITUITARY GLANDS  Function of hypothalamus Maintain homeostasis by controlling the endocrine and autonomic functions HYPOTHALAMUS Others: body temperature regulation, appetite and weight, childbirth, growth, breast milk production, sleep-wake cycle, sex drive, emotion and behaviour Disorders of hypothalamus affects many physiological function HYPOTHALAMIC DYSFUNCTION  Causes  Brain surgery, traumatic brain injury, brain tumour, genetic disorders, radiation, chemotherapy, etc  Majority of the hypothalamic dysfunction syndromes affect the hypothalamic-pituitary- adrenal axis  Disorders that produce hypothalamic hyposecretion will cause pituitary hyposecretion, vice versa  Disorders affecting hypothalamus will also affect ADH and oxytocin. HYPOTHALAMUS & PITUITARY GLANDS Hypothalamus & pituitary glands – closely connected – provide communication between brain and many of the body’s endocrine organs Hypothalamus – uses nervous input & metabolic signals from the body to control the secretion of pituitary hormones that regulate growth, thyroid function, adrenal activity, reproduction, lactation & fluid balance. PITUITARY HYPOSECRETION VS PANHYPOPITUITARISM Reduce secretion of ONE or SOME of the anterior pituitary Pituitary hormones hyposecretion Sign and symptoms based on which hormones are under secreted Onset gradual and dependent on the specific hormone deficiencies Reduce secretion of ALL anterior pituitary hormones A wide range of sign and symptoms due to comprehensive Panhypopituitarism hormonal deficiencies Onset more sudden   Complete or partial loss of anterior and posterior pituitary PANHYPOPITUITARI function SM  Complex disorder characterized by multiple hormone deficiencies – ACTH, gonadotrophin, GH, hypothyroidism  Primary or secondary  Replacement of specific pituitary hormones – glucocorticoids, thyroid hormone and sex steroid, GH  Lifelong replacement therapy & constant monitoring of multiple homeostatic function DIAGNOSING HYPOPITUITARISM Blood test Stimulation/ Brain imaging Vision test Dynamic testing To detect low To detect hormone To detect a pituitary To determine if the hormone levels levels after taking tumour or other pituitary tumour has hormone medication anormality impacted your vision PANHYPOPITUITARISM Of the deficiencies in panhypopituitarism patients: ALWAYS TREAT ADRENAL Insufficiency FIRST = steroids Replacement for Secondary hypothyroidism Secondary hypogonadism GH deficiency Should only be done AFTER (or at least concurrent with) STEROID replacement Replacement for posterior pituitary deficiencies too PITUITARY HYPOSECRETION: GROWTH HORMONE DEFICIENCY (GHD)  Aka dwarfism (pituitary dwarfism)  Dwarfism (restricted growth)- a final adult height of 4’10” (125 cm)  Children with GHD have abnormally short stature with normal body proportion  Childhood onset or adult onset  Congenital or acquired or idiopathic Investigations Recombinant hGH PITUITARY HYPERSECRETION: GIGANTISM & ACROMEGALY  Gigantism  Occurs when GH hypersecretion occurs before the fusion of the long bone epiphysis  Characterised by tall stature  Acromegaly  Occurs when GH excess occurs in adult life after the fusion of epiphysis  Characterised by large extremities and characteristic facies  If hypersecretion starts in adolescence & persists into adult life then the two conditions may be combined  Soft tissue overgrowth affecting many body systems ---signs and symptoms gradually progress over 7-10 years ADDITIONAL RESOURCE  https://www.youtube.com/watch?v=U5VVSCVJt_w INVESTIGATIONS GH concentration > 1 IGF-1 serum Glucose intolerance CT scan & MRI – mcg/L following OGTT concentrations will be present in up to 50% of presence of pituitary elevated patients adenoma  01 02 03 04 05 Remove or Restore GH Restore Improve the Retain shrink the secretory serum total signs and normal pituitary patterns to IGF-I levels symptoms pituitary mass normal to normal of disease secretion of other hormones GOALS OF THERAPY SOMATOSTATIN ANALOGS OR SOMATOSTATIN RECEPTOR LIGANDS (SRL)  Octreotide, lanreotide, pasireotide  Analogs of naturally occurring somatostatin with similar pharmacological actions but with prolonged duration of action  1st line- more effective than dopamine agonist  Available in long-acting release (IM) & short acting SC preparations  May combine with dopamine agonists to improve therapeutic efficacy  Bind to somatostatin receptors on GH-secreting adenomas & reduces GH production  Decrease GH concentrations to < 5 mcg/L & normalizing IGF-1 in 50-60% patients SOMATOSTATIN ANALOGS OR SOMATOSTATIN RECEPTOR LIGANDS (SRL)  6-month trial – 70% patients experienced significant relief of headaches, 50-75% patients –improvement of excessive perspiration, fatigue, joint pain and cystic acne.  Octreotide ---Somatostatin analogues work on somatostatin receptors to inhibit GH release  Initially 100 mcg q8H or [50 mcg q8H then increase the dose to 100 mcg q8H after 1/52- improve patient tolerance and GI side effects]  SC for at least 2/52 --- can be converted to long-acting depot  Initial long-acting: 20 mg IM every 28 days x 2-3 mth  Lanreotide – extended-release DOPAMINE AGONISTS Preferred agent in pts with coexisting hyperprolactinemia May be combine with somatostatin analog Bind to D2 dopamine receptors expressed on GH-secreting adenoma & reduces GH production Decrease GH secretion in 10-15% of patients Bromocriptine, pergolide, cabergoline and lisuride Review of 34 studies concluded bromocriptine was effective in suppressing serum GH levels to < 5 mcg/L in around 20% of patients, 10% - normalization of IGF-1, > 50% --improvement in acromegalic symptoms Usual dose 20-30mg/day in divided doses with food, 4-8 weeks DOPAMINE AGONISTS Must be started at low dose, 1.25 mg at bedtime (BROMOCRIPTINE- and increased by 1.25 mg increments every 3-4 days as needed ORAL) May initially cause headache, lightheadedness, dizziness, nervousness, fatigue & postural hypotension especially if too large a dose is given Maintenance therapy - constipation GROWTH HORMONE RECEPTOR ANTAGONIST (PEGVISOMANT)  Genetically engineered GH derivative that binds to but does not activate GH receptors and inhibits IGF-1 production by the liver, blocks physiologic effects of GH on target tissues  Dose –dependent normalization of IGF-1 concentrations in 54-89% patients after 12 weeks of therapy and in 97% patients after 1 year of therapy  SC – 40 mg loading dose, subsequently 10 mg daily  Dose adjustment – 5 mg increments based on IGF-1 concentrations every 4-6 weeks, max daily dose 30 mg  Expensive, last line, surgical and pharmacotherapy failure  Sull response - - partial response Two response HYPERPROLACTINAEMIA  A state of persistent serum prolactin elevation (> 20 mcg/L in women and > 25 mcg/L in men)  Usually affects women of reproductive age chile long tool? , gynomaster  sychiatric can't drugs se ↑ halted must immediategut , no iffrage auses hy perprolactinemia ,a stopt dry th another drugof the same gro a  Investigations test -pregnant  Omar Serri et al. CMAJ 2003;169:575-581 ©2003 by Canadian Medical Association Approach to diagnosis of hyperprolactinemia. Approach to management of hyperprolactinemia. TREATMENT – SPECIFIC CAUSE Renal failure– Discontinue Hypothyroidism-- treat underlying offending -T4 replacement cause (dialysis, medication renal transplant)  Dopamine agonists- more effective than transsphenoidal surgery Long term cure rate – microprolactinomas (60%) and macroprolactinomas (25%) SURGERY OR RADIATION Reserved for patients who cannot tolerate therapy with dopamine agonists and for patients with very large tumours Radiation therapy – several years for effective tumour shrinkage - used in conjunction with surgery DOPAMINE AGONISTS  Effective in normalizing prolactin serum concentrations, restoring menstruation & reducing tumour size 80-90% within 3 months of therapy  Bromocriptine- mainstay treatment  Cabergoline- long-acting dopamine agonist- agent of choice for prolactinomas  Decreases serum prolactin concentrations within 2 hours of oral administration, maximal suppression after 8 hours persist for up to 24 hours  Normalises prolactin serum concentration, restores gonadotrophin production and shrink tumour size- microprolactinomas (90%) ad macroprolactinomas (70%)  Pergolide, cabergoline ASSESSMENT OF THERAPEUTIC OUTCOMES Prolactin serum concentration should be monitored every 4 weeks after initiation of dopamine agonist’ Symptoms eg headache, visual disturbances, menstrual cycle, sexual function Once prolactin concentration have normalised and clinical symptoms have resolved with dopamine agonist- monitor every 6-12 months Long term treatment- dose can be gradually reduced or discontinued Microprolactinomas- normal serum concentration + 50% reduction in tumour size – medical therapy withdrawn 2-5 years