hypopituitarism

Question 1

approach to dx and management

Answer 1

-The goal is always to maintain homeostasis
-Using physiology and pathophysiology to explain the symptoms and signs.
-What if any, are the risk factors, that might result in the pathology?
-How would you approach treating the symptoms and signs?
-What does follow up entail?
-How would you explain it to the patient?

Question 2

hypopituitarism

Answer 2

-Endocrine deficiency syndromes
-Partial or complete loss of Ant. Pit. Function
-With or without associated mass lesions
-Various clinical features – depends on hormones affected

-Diagnosis:
-Imaging tests
-Measurement of pituitary hormone levels -> Basally and after various provocative stimuli

-Treatment d/o cause:
-Removal of any tumor/suppression medications
-Administration of replacement hormones

Question 3

pituitary tumors

Answer 3

-adenoma
-craniopharyngioma

Question 4

infarction or ischemic necrosis

Answer 4

-hemorrhagic infarction (pituitary apoplexy)
-shock- sheehan’s syndrome
-vascular thrombosis or aneurysm

Question 5

inflammatory processes

Answer 5

-Meningitis
-Pituitary abscess
-Sarcoidosis

Question 6

infiltrative disorders

Answer 6

-Hemochromatosis
-Langerhans’ cell histiocytosis- (Hand-Schüller-Christian disease)

Question 7

primary hypopituitarism

Answer 7

-Pituitary tumors
-Infarction or ischemic necrosis
-Inflammatory processes
-Infiltrative disorders
-Iatrogenic - removal
-Autoimmune dysfunction

Question 8

secondary hypopituitarism

Answer 8

-Hypothalamic tumors
-Inflammatory diseases
-Neurohormone deficiencies of the hypothalamus
-Iatrogenic
-Trauma

Question 9

mortality/morbidity of hypopituitarism

Answer 9

-Descending order of importance
-ACTH > TSH > GH > FSH/LH
-Deficiency of ACTH with adrenal crisis or TSH with myxedema may be life threatening -> Sudden loss of production may result in more profound morbidity than slowly progressive deficiency
-GH deficiency causes more morbidity in children than in adults
-Gonadotropin deficiency with hypogonadism may cause morbidity insidiously
-Morbidity is more profound in congenital hypopituitarism

Question 10

symptoms and signs of hypopituitarism

Answer 10

-depends on underling disorder and specific pituitary hormones (deficient or absent)
-onset- usually insidious -> may not be recognised by the pt
-occasionally onset is sudden or dramatic
-MC GH is lost first -> then gonadotropins -> then TSH and ACTH
-ADH deficiency- rare in primary pituitary ds -> common with stalk and hypothalamic lesions
-panhypopituitarism

Question 11

other presenting features of hypopituitarism

Answer 11

-attributable to the underlying cause
-a pt with space occupying lesion may present with headaches or visual field deficits
-a pt with large lesions involving the hypothalamus may present with polydipsia and syndrome of SIADH

Question 12

investigation

Answer 12

-ideally MRI
-high resolution CT
-with or without contrast (R/O structural abnormalities)
-if deficiency +ve -> potentially life threatening:
-coritsol- in ACTH deficiency
-T4, TSH:
-both are low in generalized hypopituitarism
-as opposed to primary thyroid deficiency -> increase TSH and low T4

Question 13

urgent treatment

Answer 13

-acute adrenal insufficiency
-requires immediate tx with glucocorticoids -> 100mg hydrocortisone IV, then 5-100mg every 6h and fluid replacement
-immediate referral for visual field loss is required -> classically a bitemporal hemianopsia
-refer immediately to an experienced neurosurgeon

-pituitary apoplexy:
-sudden enlargement of the pituitary, owing to hemorrhage or necrosis, with associated function loss
-Risk of catastrophic adrenal failure, visual field loss, and raised intracranial pressure
-Treat as above

Question 14

tx of hypopituitarism

Answer 14

-Hormone replacement of the hypo-functioning target glands

-Tumor
-Transsphenoidal removal or irradiation
-Dopamine agonist - often the initial treatment of prolactinoma

-Pituitary apoplexy
-Immediate surgery warranted if
-Visual field disturbances
-Oculomotor palsies
-Somnolence progresses to coma because of hypothalamic compression

-Although management with high-dose corticosteroids and general support may suffice in a few cases, transsphenoidal decompression of the tumor should generally be undertaken promptly

Question 15

DDx of generalized hypopituitarism

Answer 15

-anorexia nervosa- maintenance of secondary sexual characteristics! (this differentiates it) despite amenorrhea -> increased levels of basal growth hormone (low IGF) and high cortisol
-alcohol liver disease of hemochromatosis- evidence of liver disease -> lab testing
-myotonia dystrophica- progressive weakness, premature balding, cataracts, facial features of accelerated aging -> lab testing
-polyglandular autoimmune disease

Question 16

hypopituitarism in children -sx,dx,tx

Answer 16

-Pituitary tumor - Craniopharyngioma
-Langerhans’ cell histiocytosis
-Midline defects -Cleft palate
-Therapeutic radiation of the CNS
-Hereditary – 5%
-Idiopathic
-Presentation:
-Height is below the 3rd percentile, and growth velocity
-Skeletal maturation > 2 yr behind chronologic age
-Fails to begin pubertal development

-Assess bone age
-X-ray of the left hand
-Skeletal maturation usually delayed to the same extent as height

-CT or MRI of brain
-R/o calcifications & tumors
-Mid to late childhood, insulin-like growth factor 1 (IGF-1) levels measured

-Treatment
-Surgery
-GH replacement
-Other hormones need to be replaced as well (Cortisol, Thyroid, gonadal sex steroids)

Question 17

GH deficiency

Answer 17

-clinically undetectable in adults
-usually, asymptomatic
-decreased energy
-?? accelerates atherosclerosis
-hypopituitarism in children
-abnormally slow growth
-short stature with normal proportions

Question 18

ACTH defieicny

Answer 18

-hypoadrenalism:
-fatigue
-weakness
-wt loss
-hypotension
-hypoglycemia
-intolerance to stress and infection
-decreased axillary and pubic hair

-no hyperpigmentation
-plasma and urinary steroid levels are low
-rise to normal after ACTH replacement
-tx is with cortisol replacement

Question 19

ACTH investigations

Answer 19

-cortisol levels alone are not reliable indicators of ACTH-adrenal axis function
-One of several provocative tests

-Standard ACTH simulation test
-Safer & less labor intensive
-Synthetic ACTH (cosyntropin)
-Administered – IV/IM
-Plasma cortisol response measured 30 and 60 min later
-Cortisol should rise significantly; Normal response is cortisol >21 g/dL and aldosterone response of >4 ng/dL above baseline

-Insulin Tolerance Test
-Hazardous test in patients with severe documented:
-Panhypopituitarism
-Diabetes mellitus
-Elderly
-Contraindicated in those:
-Coronary artery disease
-Epilepsy

Question 20

lack of LH and FSH

Answer 20

-in children- delayed puberty, short stature
-premenopausal women:
-amenorrhea
-reduced libido
-regression of 2ndary sexual characteristics
-infertility

-men:
-ED
-testicular atrophy
-reduced libido
-regression of 2ndary characteristics
-decreased spermatogenesis with consequent infertility

Question 21

kallmann’s syndrome

Answer 21

-Specific lack of gonadotropin-releasing hormone (GnRH)
-Associated with midline facial defects
-Anosmia
-Cleft lip or palate
-Color blindness
-hypogonadism and anosmia or hyposmia
-1/2 of these pts have unilateral renal agenesis (missing a kidney)
-some pts also exhibit cryptochidism (testes dont descend), micropenis, color blindness, sensorineural deafness, cerebellar ataxia, cognitive problems, bimanual synkinesis (mirror movement), cleft lip or palate, or high arched palate
-some affected women have menarache followed by secondary amenorrhea

Question 22

panhypopituitarism

Answer 22

-simmond’s syndrome
-involvement of all pituitary hormones -> only one or more pituitary hormones are often involved resulting in partial hypopituitarism

Question 23

panhypopituitarism: sheehan’s syndrome**

Answer 23

-affects postpartum women
-loss of blood after delivery
-after delivery of placenta uterus can contract fully
-when placenta isnt fully delivered, laceration,
-amount of blood loss depends on if pt is anemic or not
-pituitary does get enough blood -> often panhypopituitarism
-pituitary necrosis from hypovolemia and shock- peripartum period
-lactation does not start after childbirth
-fatigue
-loss of 2ndary sexual characteristics- loss of pubic and axillary hair (DIFFERENTIATES FROM ANOREXIA)

Question 24

pituitary apoplexy

Answer 24

-adrenal crisis
-sudden onset
-pituitary outgrows the blood supply
-sx complex caused by hemorrhagic infarction of either a normal pituitary gland or, more commonly a pituitary tumor
-symptoms:
-severe headache
-stiff neck
-fever
-visual field defects
-oculomotor palsies

-resulting edema due to compression of hypothalamus- somnolence or come
-varying degrees of hypopituitarism may develop suddenly- many present with vascular collapse bc of deficiency ACTH and cortisol
-CSF +/- blood
-MRI- hemorrhage