What is Acromegaly?

Acromegaly is an abnormal hypertrophy of the body and internal organs caused by excessive secretion of growth hormone (GH) from the pituitary gland, and is accompanied by corresponding endocrine and metabolic diseases with abnormal physiological functions.

Basic Information

English name: Acromegaly
Visiting department: Orthopedics, neurology, endocrinology
Common locations: Hands, feet

Common causes: Caused by excessive secretion of growth hormone (GH) from the pituitary
Common symptoms: Rough face, headache, fatigue, sweating, backache, widening of hands and feet, etc.

Acromegaly classification

1. Non-GHRH dependent

Of the vast majority, elevated GH inhibits hypothalamic GHRH release through a negative feedback mechanism; more than 95% are pituitary GH adenomas, and very few are ectopic GH tumor secretions (lung cancer and pancreatic cancer, etc.).

2.GHRH dependent

Mainly due to ectopic tumors of the hypothalamus or other visceral tumors that produce GHRH, stimulate the anterior pituitary hyperplasia and secrete too much GH.

Causes of Acromegaly

Increased secretion of growth hormone during childhood and adolescent illness can cause delayed epiphyseal closure and accelerated growth of long bones to cause giant disease; post-pubertal epiphysis has merged to form acromegaly; a few adolescents from onset to adulthood continue to develop giant disease.

GH secretion from the anterior pituitary gland is controlled by GHRH (growth hormone releasing hormone) produced by the hypothalamus and somatostatin produced by the hypothalamus and pancreas. After entering the circulation, GH can stimulate the liver to synthesize insulin-like growth factor (IGF, growth interleukin), which can cause fingertip hypertrophy, bone and joint hyperplasia, myocardial hypertrophy, visceral hyperplasia, insulin resistance, colon polyps, and tumorigenesis.

Multihormone-secreting GH adenomas can simultaneously secrete PRL (prolactin), TSH (thyroid stimulating hormone), and ACTH (corticotropin-releasing hormone); GH adenomas can be associated with McCune-Albright syndrome (multiple osteofibrosis, Skin coffee spots and precocious puberty, etc.) can also be accompanied by MEN-1 (multiendocrine adenoma type 1), Carney syndrome (cutaneous and cardiac myxoma, Cushing syndrome and GH adenoma).

Clinical manifestations of acromegaly

In the early stage (formation period), the body and internal organs are generally hypertrophic, with anterior pituitary hyperfunction; in the late stage (decay period), physical decline occurs, and secondary anterior pituitary hypofunction occurs.

1. This disease is rare and occurs in young and middle-aged men. The average age of onset is 40 to 45 years. Generally, the onset is relatively slow and the course is longer, which can reach more than 30 years.

2. Childhood-developed GH adenoma manifests as giant disease; adult-onset patients mainly present with space-occupying effects and endocrine disorders, such as rough faces, headaches, fatigue, sweating, back pain, enlarged hand and foot widening, hats and Increasing shoe size can also show symptoms and signs of diabetes and hyperthyroidism:

(1) Extremities of the skeletal and muscular system are hypertrophic, the jaw is too large, the upper jaw is widened, the forehead is raised, the nasal hyperplasia and hypertrophy, and the paranasal sinuses are enlarged. Single or multiple non-inflammatory osteoarthropathy, reduced sex hormones cause bone Loose.

(2) Skin Oily skin, sweaty, rough body hair, rough face, thickened fingers, skin wrinkles and heel hypertrophy.

(3) Cardiovascular system Atherosclerosis, left heart hypertrophy, enlarged heart, high blood pressure, cardiovascular and cerebrovascular diseases, myocardial mononuclear cell infiltration and interstitial fibrosis. Early in the state of high circulatory dynamics, such as increased heart rate, increased stroke volume, and decreased vascular resistance; subclinical cardiomyopathy in young patients without hypertension and normal glucose tolerance is manifested by bilateral ventricular diastolic dysfunction at rest and during exercise Impaired heart function; 20% of patients have symptomatic cardiovascular disease at the time of diagnosis, such as hypertension, coronary heart disease, arrhythmia, conduction block, heart valve disease, etc. Lowering GH and IGF can improve these symptoms.

(4) Respiratory system Hypertrophy of the upper respiratory tract mucosa and soft palate and hypertrophy of the tongue muscles cause sleep apnea and snoring; hypertrophy of the vocal cords causes narrowing of the glottis and difficulty in intubation.

(5) 50% of the nervous system has sensory and motor polyneuritis, with gloves and cuff-like distribution, focal paralysis of peripheral nerves, proximal muscle weakness and convulsions, carpal tunnel syndrome and plasma CPK (creatine phosphokinase ) Elevation, depression, inattention, anxiety, etc.

(6) More than 50% of the endocrine system has amenorrhea or impotence, 30% have hyperprolactinemia, and 25% have secondary thyroid or adrenal insufficiency; polyhormone-secreting tumors cause hyperthyroidism, thyroid hyperplasia, or tumors; prepuberty Of children showed linear growth, giant disease, and precocious puberty; adolescent children showed rapid growth, amenorrhea, or low sexual function, often accompanied by headache and visual impairment, and half of the children had hyperprolactinemia or pituitary insufficiency.

(7) Metabolism of 20% to 30% occurs insulin resistance, impaired glucose tolerance, or induces diabetes; can promote amino acid conversion and protein synthesis; increase blood lipids; antidiuretic effects increase body fluids and extracellular fluids, cause hypertension; promote gastrointestinal The absorption of calcium causes an increase in serum calcium and phosphorus, an increase in urine calcium and phosphate, an increase in urinary stones and bone density.

(8) Tumors The high incidence of colon, rectal adenoma, and cancer may be related to the excessive proliferation of intestinal epithelial cells, and the incidence of thyroid tumors is also increased.

(9) Pituitary dysfunction manifestations Sexual dysfunction, general weakness, impotence, amenorrhea, atrophy of the sexual genitals.

(10) Pregnancy and reproduction Male patients may have hypersexuality at an early stage, and later sexual function disappears; women have irregular menstruation or amenorrhea, hyposexuality or disappearance, breast milk, etc .; ovulation, conception and pregnancy rate are low, and hypertension is prone to occur during pregnancy , Coronary heart disease and other complications.

3. Common clinical symptoms and signs include face changes, enlarged extremities, soft tissue swelling, sweating, limb numbness / carpal tunnel syndrome, fatigue, burnout, headache, menstrual disorders, amenorrhea, infertility (female), impotence, sexual desire Impaired (male), arthropathy, impaired glucose tolerance / diabetes, goiter, ear, nose, mouth and throat symptoms, congestive heart failure / arrhythmia, hypertension, visual field loss.

4. The disease is mostly caused by pituitary growth hormone adenoma, which accounts for about 20% of all pituitary tumors, of which 75% are pituitary adenomas. Therefore, in addition to the above-mentioned endocrine manifestations, patients often have headaches and double temporal fields Hemiblindness and other signs of pituitary adenomas on the compression of peripheral nerve structures.

Acromegaly diagnosis

Mainly based on the patient's medical history, typical clinical manifestations, visual function and other nervous systems, and endocrinology and imaging examinations to determine whether there is a pituitary growth hormone adenoma, and its size and location (in the saddle, upper saddle, and next to the saddle) , Posterior saddle, under saddle), with or without invasion of cavernous sinus and surrounding tissues, understand the tumor's biological activity, hormone secretion characteristics and pathological types. Specifically, it should include:

(1) Detailed medical history.

(2) The above typical clinical manifestations.

Imaging of acromegaly

1.X-ray butterfly saddle

Swollen saddle (normal anteroposterior diameter 7-16mm, deep diameter 7-14mm, wide diameter 9-19mm), bone absorption or destruction of saddle bottom, invasion of saddle dorsal bone, tilt of saddle bottom showed bilateral sign (lateral position).

2. Thin layer (1.5mm) section CT

Coronal and sagittal reconstructions and axial scans in the sphenoid region revealed only 30% of microadenomas <5mm. Most tumors are low-density shadows, which are uniformly strengthened or peripherally strengthened (necrosis of the tumor center or cystic degeneration of peripherally strengthened tumors with different thicknesses); they can protrude into the upper saddle with pituitary stalk offset, and can penetrate the bottom of the saddle to form sphenoid sinus Inner lump. Indirect signs include enlargement of the saddle, tilting of the saddle bottom, thinning and destruction of peripheral bone resorption.

3.MRI (magnetic resonance imaging)

The advantage is that GD-DTPA is safer than CT-enhanced iodinating agents and has less allergic reactions; the disadvantage is that it cannot show changes in the surrounding skull. The key to diagnosis is a thin-layer coronary T ₁ weighted image scan, but the detection rate of micro adenomas <5mm is only 50% to 60%. Dynamic enhanced scanning can improve the detection rate; T ₁ WI is low signal and T ₂ WI High signal, proton density weighted image is equal signal; the larger T ₁ WI is low or equal signal, T ₂ WI is equal or higher signal; significantly enhanced after GD-DTPA injection; pituitary stalk offset, saddle bottom Inclined, the tumor protruded into the upper saddle pool, interventricular foramen, third ventricle, and invaded the frontal lobe, temporal lobe, sphenoid sinus, ethmoid sinus, cavernous sinus, interpodal cistern, and anterior bridge cistern.

4. Detection of growth hormone levels

The basal level of GH was positively correlated with tumor size, degree of invasion, and surgical effect. The normal level of GH in the resting state after fasting for 12 hours is (2 4) g / L, and the upper limit of the normal reference value for the basic blood GH in the morning is 5 g / L; about 90% of GH adenoma blood GH> 10 g / L. Monoclonal antibody method for patients with acromegaly is often more than 50 times higher than normal.

5. Oral glucose tolerance test (OGTT)

The value of a single measurement within a single time is not significant. Generally, an oral glucose suppression test is used (GH value should be decreased 2 hours after normal oral administration of 100 g glucose, and it should rise after 3 to 4 hours). Patients with GH adenomas are in an uninhibited state and irradiated with insulin or THR did not increase GH in excitatory tests. Oral glucose tolerance test for normal people should be <2g / L, ultrasensitive radioimmunoassay method should be L; GH adenoma biochemical method should be> 0.4g / L, GH> 1 2g / L, IGF-1 <during OGTT 1 g / L.

6. Octreotide and diethylenetriamine pentaacetate (DTPA) combined with ¹¹¹ In scintigraphy

Pituitary adenomas can be displayed by labeling growth hormone receptors.

7. Other

Blood biochemistry, urine routine, blood cell count, etc.

Differential diagnosis of acromegaly

1. The appearance of acromegaly needs to be distinguished from cutaneous periosteum hypertrophy. The X-ray manifestations of the latter are: periosteal hyperplasia of the extremities and thickening of the backbone, which are symmetrical, mainly tibia and fibula and ulna and radius. The periosteum was serrated early, and connected to each other in layers as the disease progressed; the periosteum was most obvious at the distal end of the diaphysis, and gradually spread to the proximal end, generally not involving the callus and metaphysis.

2. Pituitary growth hormone adenomas are mainly distinguished from the following diseases:

(1) Other tumors of the saddle region, such as craniopharyngioma, meningiomas, gliomas, germ cell tumors of the saddle region, chordoma, epidermoid cysts or dermoid cysts of the saddle region, Schwann cell tumors, metastases, and nerves Pituitary tumors, primary or secondary symptoms of saddle area caused by leukemia, lymphoma, and plasmacytoma.

(2) Congenital malformations in the saddle area or other non-tumorous lesions such as Rathke cysts, empty saddles, arachnoid cysts in the saddle area, internal carotid artery and anterior cerebral artery or anterior communication aneurysm, and traffic hydrocephalus. Third ventricle enlargement and so on.

(3) Pituitary abscesses, arachnoid adhesions, tuberculous meningitis and mucus cysts, inflammatory diseases in the saddle area, fungal infections in the saddle area, toxoplasma pneumocystis infection in patients with AIDS, lymphocytic pituitary inflammation, Langerhans Histiocytosis.

Acromegaly Complications

Local

Headache, visual field defect, neuropathy, hydrocephalus, and temporal lobe epilepsy.

2. Whole body

(1) Cardiovascular system Myocardial ischemia, cardiomyopathy, congestive heart failure, arrhythmia, hypertension.

(2) Respiratory system Humpback and barrel chest, sleep apnea.

(3) Central nervous system stroke.

(4) Metabolism Diabetes, impaired glucose tolerance (insulin resistance), hyperlipidemia (triglycerides).

(5) Tumors Colon and rectal, breast and prostate tumors.

(6) Bone degenerative osteoarthropathy, calcium deposits, pyrophosphate arthropathy.

Acromegaly Treatment

Surgical treatment

(1) Transsphenoidal pituitary adenectomy There is no obvious indication of grade , , , or 0 or A tumors that expand on the saddle, especially tumors with active endocrine function; that obviously invades the sphenoid sinus Grade IV tumors, no obvious vision, visual field changes or slight changes; Grade E tumors invading cavernous sinus, no obvious vision, visual field changes; obvious grade A to B tumors on the saddle, no severe vision Lesions, enlarged saddle and saddle septum enlargement (coronary scan tumors are oval rather than dumbbell-shaped), and the mass on the saddle is located strictly in the midline and is bilaterally symmetrical. Contraindications Nasal infection or chronic sinusitis, mucosal congestion; A-media type with minor or poor sphenoid sinus vaporization; small saddle septum, coronal scan shows dumbbell-shaped mass on saddle and saddle, saddle The upper mass is not easy to be removed. The mass is large (Grade C) or spreads to the anterior, middle and posterior concavity (Grade D). Surgical approach is through the sub-lip-nasal septum-sphenoid sinus approach; transnasal vestibular-nasal septum-sphenoid sinus approach; transethmoidal-sphenoid sinus approach; direct transnasal sphenoid sinus approach. Postoperative treatment Antibiotics (2 weeks), generally do not use dehydrating agents and hormones, if necessary, hormone replacement therapy (such as ACTH adenoma), diabetes insipids are given pituitary antidiuretic hormone. Major complications: Cerebrospinal fluid leakage, meningitis, diabetes insipidus.

(2) Transcranial pituitary adenoma resection Indications Those whose tumors develop to the level above the saddle reach level B or C; those whose giant pituitary adenoma develops above the saddle and the saddle does not expand; those above and below the saddle septum The tumor mass is dumbbell-shaped growth; the tumor on the saddle grows to the anterior, middle, and posterior concave (D1, D2, and D3 tumors); the lobular tumor on the saddle. Surgical approach : Subfrontal (intradural) approach; subfrontal and epidural approach; transwing approach; subfrontal and wing approach; unilateral infratemporal epidural cavernous sinus approach Approach; inter-brow-anterior skull base approach; supraorbital keyhole approach; unilateral transorbital, forehead, and butterfly approach. Postoperative treatment Dehydration and hormonal treatment, symptomatic treatment of hypopituitarism, diabetes insipidus, high fever, coma, gastrointestinal bleeding, etc.

2. Radiation therapy

(1) Traditional radiotherapy Mostly use fractional radiation therapy (45 ~ 55) Gy / (4 ~ 5) w, which may have delayed hypopituitarism, vision loss, temporal lobe radiation necrosis, vascular damage, cognitive memory impairment And secondary tumors.

(2) Gamma knife radiotherapy has the most advantages, can control the hormone levels of secreted tumors, improve clinical symptoms; reduce or control tumor growth; protect normal pituitary tissue. Peripheral dose of nonfunctional adenoma can control growth of 10-12Gy, growth hormone adenoma needs 30Gy to control clinical symptoms; PRL adenoma needs more than 30Gy; ACTH adenoma can control growth and improve levels of 23-34Gy; generally considered to normalize hormone levels The dose is at least 35Gy.

(3) X-knife has poor accuracy and high complications.

3. Drug treatment

(1) Dopamine stimulants Bromocriptine and cabergoline can improve symptoms in patients with acromegaly, but they cannot restore serum GH and IGF-1 levels to normal.

(2) Somatostatin octreotide.

Prognosis of acromegaly

The common deaths in patients with acromegaly are due to cardio-cerebral vascular disease, dyspnea, diabetes, and colon tumors. The mortality rate is related to GH levels (GH> 10ng / ml).