Introduction to Endocrinology.

Hypothalamic and

Pituitary diseases

Prolactinoma + Acromegaly

Dr. Peter Igaz MD PhD DSc

2nd Department of Medicine

Semmelweis University

Fields of Endocrinology

• Diseases of the pituitary (Hypothalamus)

• Thyroid

• Parathyroid

• Adrenal diseases

• Gonads/reproductive endocrinology

• Diabetes mellitus

• Multiple endocrine Neoplasias

• Autoimmune polyendocrine syndromes

Principles of Endocrinology

• Primary vs. Secondary (pituitary)

dysfunctions (Tertiary)

• First – laboratory investigations, then

imaging

Causes of hypothalamic dysfunction

• Tumors (astrocytoma, glioma, germinoma, craniopharyngeoma, large pituitary tumor, lymphoma)

• Haemorrhages

• Developmental abnormalities (arachnoideal cyst, holoprosencephaly)

• Granulomatous inflammation (histiocytosis X, sarcoidosis, TBC)

• inflammation (encephalitis, meningitis)

• Trauma

• Irradiation

• Hereditary diseases

Diseases of the hypothalamus

• Deficiency of trophormones (CRH, TRH, GnRH, GHRH) – growth failure, hypopituitarism, disorders of sexual development (isolated GnRH-deficiency – Kallmann-syndrome)

• Deficiency of posterior pituitary hormones

• Non-endocrine consequences of hypothalamic damage: – Feeding disorders (anorexia, hyperphagia, obesitas)

– Disorders of fluid intake (adipsia, polydipsia)

– Disorders of thermoregulation (hyperthermia, hypothermia)

– Somnolentia, coma, lightmindedness

– Mood lability

Hypothalamic forms of obesity

• Dystrophia adiposogenitalis (Fröhlich-syndrome)

– obesity, hypogonadism, visual disturbances, skeletal malformations, white skin, intracrnaial tumor

• Laurence-Moon-Biedl syndrome (AR, 1:160.000)

– Laurence-Moon: obesity, spastic paraparesis, retinitis pigmentosa, mental retardation, hypogonadis

– Biedl-Bardet: polydactily, retinitis pigmentosa, mental retardation, hypogonadism, renal malformations

• Prader-Willi-Labhart syndrome

Diseases of the pituitary

• Adenomas (Micro-, Macro-, Incidentaloma)

• Anterior pituitary

– Hormone overproduction (60-70%)

• Prolaktin

• GH

• ACTH

• TSH (very rare)

– Hormonally inactive pituitary tumors (also the

gonadotropin-secreting) (30-35%)

Hypopituitarismus

• Posterior pituitary

– Diabetes insipidus

– SIADH

Micro- and Macroadenoma

• Limit: 10 mm

• Consequences:

– Hormone overproduction

– Mass effects

• Vision loss

• Hormon losses (1. GH, 2. LH/FSH, 3. TSH, 4. ACTH)

• increased Prolactin (Stalk lesion)

• Intracranial hypertension

• Neurological Complications

• Mostly benign, pituitary cancer is extremely

rare, defined by the presence of

intracerebral metastases

Frequency of pituitary adenomas

Pituitary tumors are the most prevalent

intracranial neoplasms – Prevalence 77/100.000

• 1. Prolactinoma

• 2. Hormonally inactive tumors (gonadotropin

secretion without clinical consequences)

• 3. GH

• 4. PRL + GH

• 5. Cushing-disease

• 6. TSH (Incidence: 1-2/10 Million/year)

Pituitary incidentaloma

• Definition: Pituitary adenomas discovered by

brain imaging MRI (or CT) that was not

indicated with the suspicion of pituitary

disease (similar definition for adrenal

incidentaloma)

• Very frequent, about 10 % of the population

has pituitary incidentalomas on MRI

(Inhomogenities of the pituitary)

• Mostly hormonally inactive microadenomas

without clinical relevance

Examination of pituitary

adenomas

• Hormonal Work-up - Screening

– Prolactin

– Cortisol, ACTH

– TSH, fT4

– IGF-1

– LH, FSH, Sexual steroids

• Imaging (MRI)

• Ophtalmological examination

Treatment of pituitary adenomas

• Surgery – Macroadenomas, Vision loss,

neurological complications,

Liquorrhoea, Hormone overproduction

(with the exception of most

prolactinomas)

• Medical treatment (Prolactinoma,

Acromegaly)

• Irradiation (gamma-knife)

Prolactinoma

• The most common form of pituitary

adenoma

• Microprolaktinoma vs.

Macroprolaktinoma (Limit 10 mm)

• Prevalence 44/100.000

• Characteristic Symptoms in women,

often without symptoms in elderly men

Symptoms of Prolactinoma

Women

• Galactorrhoea

• Amenorrhoea/

Raromenorrhoea

• Osteoporosis

• Mass effects – both genders

• Vision loss

• Hormone losses

• Neurological complications

Men

• Loss of libido

• Impotence

• Osteoporosis

Normal Prolactin levels

• Normal range: 5-20 ng/ml

• Prolaktin levels associated with Prolactinoma are

mostly >200 ng/ml.

• In case of macroprolactinoma, PRL is usually

>1000 ng/ml.

• Hook-Effect – in case of very high PRL levels,

laboratory measurement can be falsely negative

• Macroprolactin – prolactin polymers – non-

functional, false positive results – PEG-Reaction is

needed to exclude it

Other causes of hyperprolactinemia

• Drugs

• Pituitary lesions (Trauma, Surgery, large

tumors (Macroadenomas), infiltrative

lesions /e.g. sarcoidosis/)

• Estrogen

• Hypothyroidism

• Trauma or irritation of the thoracic wall

• Chronic renal insufficiency

Drugs causing hyperprolactinemia

• Dopamin-antagonists (D2-Receptor

Antagonists)

• Antipsychotic Drugs – Risperidone

• Antidepressives

• Antiemetic drugs – e.g. Metoclopramide

• Antihypertensive drugs (Verapamil,

Reserpin, Methyldopa)

Macroprolactinoma

Treatment of Prolactinoma

• Drug treatment– Dopamin Agonists

– Bromocriptin – Ergot-Derivative

– Quinagolid

– Cabergolin - Ergot-Derivative

Surgery – threatening vision loss, neurologic

consequences, ineffective drug treatment,

missing compliance

Irradiation

Acromegaly and Gigantism

Rare disease

Prevalence: 30-70/Million

Symptoms of Acromegaly

• Growth of the „Acras”: Hands (Sausage

fingers), Legs, Nose, tongue (Macroglossia),

Ears, Lips, Carpal Tunnel syndrom

• Hand shoe size? Shoe size?

• Visceromegaly (Cardiomegaly) – Hypertension,

Heart insufficiency, Sleep apnoe

• Increased tumor incidence – Colon polyposis,

Colorectal Cc.

• Sweating

• Diabetes mellitus

• Endocrine dysfunctions (Raromenorrhoea,

Impotence)

Death causes in acromegaly

• Cardiovascular (Heart insufficiency)

60%

• Respiratory (25 %)

• Tumor disease (15%)

Laboratory diagnosis of Acromegaly

• Screening – Serum IGF-1

• Confirmation- OGTT (Oral glucose

tolerance test) – 75 g Glucose per os,

Blood taken at 0’, 30’, 60’, 90’, 120’, 180’

• Normally GH goes below 1 ng/ml, in

acromegaly it remains over 2 ng/ml, and a

paradoxical increase of GH can even be

observed

Treatment of acromegaly

• 1. Surgery

– Success rate for microadenomas: 70-90%

– Success rate for macroadenomas: 50-70%

• 2. Drug treatments

– Somatostatin Analogues (Octreotid,

Lanreotid, Pasireotid)

– GH-Receptor antagonist, Pegvisomant

(Somavert)

– Dopamin agonists (Cabergolin)

• 3. Irradiation