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