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