ED yr V Internal diseases, endocrinology Diseases of pituitary and hypothalamus Prof. Marek Bolanowski, M.D., Ph.D. Department of Endocrinology, Diabetes and Isotope Therapy Wrocław Medical University
ED yr V
Internal diseases, endocrinology
Diseases of pituitary and
hypothalamus
Prof. Marek Bolanowski, M.D., Ph.D. Department of Endocrinology,
Diabetes and Isotope Therapy
Wrocław Medical University
Pituitary tumors
Hypopituitarism
Diabetes insipidus
Pituitary tumors adenomas
Monoclonal, slowly growing, benign neoplasms
• clinical 0.02-0.025% but autopsy 10-20%
Hormonally active
• prolactin - prolactinoma - 50%
• GH - acromegaly - 20%
• ACTH - Cushing’s disease - 10%
• TSH, LH, FSH, α-subunit
Hormonally inactive - 20%
Other pituitary tumors
• Craniopharyngioma
• Glioma, chordoma
• Germinoma, dysgerminoma
• Metastatic
Metastatic tumors to the pituitary
• breast 50%
• lung 20%
• gastrointestinal tract 6-10%
• prostate 6-10%
• melanoma 2%
• other 8-16%
Pituitary tumors
• presence of endo- or exogenous stimulatory
factors/lack of inhibitory factors
• receptor defects, mutations, protooncogenes
activation, second messenger disturbances
• differentiation of stem cells
• clone expansion
• tumor formation
11q13 chromosome deletion in MEN-1, only
Pituitary tumors
Mass effects
• headache and visual disturbances: visual loss, visual field deficit, optic pallor, ocular dysmotility, pupillary abnormalities
Radiological
• sella enlargement, erosion of dorsum
• calcifications in the tumor
Hormonal
• hormonal excess/deficit
• diabetes insipidus
Pituitary adenomas Pituitary adenomas
• microadenomas < 10 mm
• macroadenomas ≥ 10 mm
Clinical presentation of
hyperprolactinemia in women
• amenorrhea and galactorrhea 81.0%
• amenorrhea 12.0%
• oligomenorrhea and galactorrhea 1.4%
• regular menses and galactorrhea 1.4%
• visual field defect 1.4%
Clinical presentation of
hyperprolactinemia in men
• loss of libido/potency 47%
• headache 13%
• visual failure 13%
• gynecomastia 6%
• galactorrhea 2%
Diagnosis of hyperprolactinemia
• Sustained hyperprolactinemia
> 20 ng/ml in women
> 10 ng/ml in men
< 200 ng/ml - microprolactinoma
> 200 ng/ml - macroprolactinoma
100-200 ng/ml – pseudoprolactinoma
• Macroprolactinemia
Macroadenoma of the pituitary
(acromegaly)
Symptoms and signs of acromegaly
• acral/facial changes 98%
• oligo/amenorrhea 72%
• excessive perspiration 64%
• headache 55%
• paresthesias/carpal tunnel syndrome 40%
• erectile dysfunction 36%
• hypertension 28%
• goiter 19%
Gigantism
Diagnostic criteria of acromegaly
• lack of GH suppression during OGTT < 1 µg/l (ng/ml)
• elevated IGF-1 level
Clinical features of Cushing’s
disease/Cushing’s syndrome
• central obesity 85%
• facial plethora 80%
• hirsutism 75%
• menstrual disorders 75%
• striae 50%
• weakness 50%
Localization tests in Cushing’s
syndrome
• ACTH
• high dose dexamethasone suppression test
• CRH stimulation test
• pituitary MRI
• adrenal CT/MRI
• inferior petrosal sinus sampling
• Cortisol profile
• Urinary free cortisol excretion
Clinical presentation of TSHoma
• goiter 94%
• visual field defects 42%
• ophthalmopathy 6%
• acromegaly 16%
• amenorrhea/galactorrhea 12%
Baseline laboratory changes in
TSHomas
• T4, T3 elevated
• TSH detectable
• α-subunit/TSH ratio > 1.0
• GH, Prl, LH, FSH elevated
Gonadotroph adenomas
• decreased visual acuity 43%
• hypopituitarism 22%
• asymptomatic 17%
• headache 8%
• combination of symptoms 10%
• testes enlargement rare
• ovarian hyperstimulation rare
Gonadotroph adenomas
• normal LH, FSH for age in women
• sometimes LH, FSH increased in men
• testosterone decreased in men
• exaggerated LH, FSH response in TRH test
Differential diagnostics
• pseudotumors / pituitary cells hyperplasia
• incidentaloma
• empty sella
• lymphocytic hypophysitis
Pituitary enlargement
• Pregnancy
• Hypothyroidism
• CRH or GHRH secretion in excess
Empty sella
Pituitary carcinoma
• rare, less than 1%
• about 100 cases in the literature
• carcinoma similar to invasive adenoma
• clinical course with frequent recurrences, treatment
resistance and manifestation of metastases
Surgical treatment
• selective, transsphenoidal adenomectomy
• repeated approaches
• transcranial surgery
The goals of neurosurgery
• complete cure
• vision preservation
• hormonal balance
Medical treatment of prolactinomas
Dopamine agonists:
• ergot derivatives
bromocriptine: Parlodel, Bromergon, Bromocorn, Ergolaktyna
1-3 times daily, 1.25-15 mg/day
pergolide, lisuride, once daily
Cabergoline: Dostinex 0.25-2 mg twice weekly
• non-ergot derivatives
quinagolide: Norprolac 37.5-150 mg/day
• The effect of
bromocriptine
treatment on
prolactinoma
Medical treatment of acromegaly -
GH secreting tumors
• somatostatin analogs
octreotide: Sandostatin, Sandostatin LAR
lanreotide: Somatuline Autogel
vapreotide
• dopamine agonists
bromocriptine: Parlodel, Bromergon
cabergoline: Dostinex
• GH receptor antagonist
pegvisomant blocks peripheral GH action
Radiotherapy of pituitary tumors
• conventional radiotherapy 40-50 Gy, fractioned in
doses 2.0-2.5 Gy at 4-5 sessions a week
• gamma unit stereotactic radiosurgery „gamma knife”
Incidentaloma
Problem of modern technology
• head trauma
• accidents
• CNS events
with a need for head CT/MRI scans
Pituitary incidentaloma
• on CT scans up to 20%
• on MR scans 10%
• autopsy 10% - 20% (micro)
Incidentaloma – management
algorithm
• hormonal function
• size, growth
• visual abnormalities presence
• other local disturbances
• generalized systemic disturbances
Pituitary incidentaloma
hormonal function assessment
functioning non-functioning
Prl GH, ACTH, macro micro
TSH, Gn visual field
function
MR
½, 1, 2, 5 years
DA
MR
surgery 1, 2, 5 years
SMSA
Hypopituitarism
• Idiopathic
• Due to pituitary tumor
• Iatrogenic
– Neurosurgery
– Radiotherapy
Hypopituitarism
• secondary hypocortisolism
• secondary hypothyroidism
• secondary hypogonadism
• GH deficiency
Secondary hypocortisolism
(ACTH deficiency)
• nausea, vomiting, abdominal pain, hypothermia
• hypovolemia, low blood pressure, postural hypotension
• asthenia, hypoglycemia
• hyponatremia, hyperkalemia
• no skin hyperpigmentation
• low ACTH, low cortisol
Secondary hypothyroidism
(TSH deficiency)
• cold intolerance, easy fatigability, weakness
• constipation, pale and dry skin, intellectual impairment
• bradycardia, slowed speech, hypothermia, oedema
• delayed relaxation of deep tendon reflexes
• low TSH and fT4
Secondary hypogonadism
(gonadotropin deficiency)
• eunuchoid proportions and sexual infantilism
(prior to puberty)
• absence of axillary and pubic hair, no breast
development
• secondary or primary amenorrhea
• impotence, loss of libido, infertility
• decrease in muscle and bone mass
• low LH/FSH, E2, T
GH deficiency
• growth retardation (prior to puberty)
• body composition changes:
adipose tissue increase,
muscles and bone mass decrease
• no GH increment following stimulation, low IGF-1
Sequence of the pituitary
hormonal deficiencies
• GH, IGF-1
• LH, FSH, E2, P, T
• TSH, fT4
• ACTH, cortisol
Necessity for hormonal replacement
Hormonal replacement
• Cortison, Hydrocortison 10-30 mg/d
• L-Thyroxine 50-150 mcg/d
• Estrogen/Progesterone
• Testosteron
• Growth hormone
Diabetes insipidus
• deficiency/lack of ADH
• kidneys insensitivity for ADH
• polyuria, polydipsia, thirst
• serum hyperosmolality > 295 mOsm/kg H20
• urine hypoosmolality
• urine specific gravity 1000-1008 g/l
Diabetes insipidus
• Desmopressin
Minirin tabl. 2 x 0.1 – 3 x 0.2 mg daily
Adiuretin nasal spay 1-2 x 10-40 µg
• Lysine-Vasopressin