Acromegaly

1
Acromegaly

• E.J. ROOD

2
Patient

• Mr J.
• 32-year-old male
• Was admitted by Dr E Du Raan from Department of
  Internal Medicine
• October 2004

3
SYMPTOMS

• Backache
• Generilsed pain and weakness in arms
• Dispnoea and palpitations
• Headaches
• For three years
• His shoe size increased from nr. 9 to nr. 11 in
  one year.

4
Clinical Examination

• Appearance of acromegaly
• Frontal bossing
• Prognatism
• Wide spaces between teeth.
• Big hands with wide fingertips
• Big feet with wide heel pad
• Prominent breastbone

5

WWW.GOOGLE-IMAGES/ACROMEGALY.COM
6

7
Clinical Examination

• CVS BP 160/100
• RESP Normal
• Abd Normal

8
Patient presents with

• Acromegaly
• Hypertension

9
Special investigations

• T4 17,7 (14,4 24,0 pmol/l)
• TSH 1,0 (0,30 5,0 mIU/l)
• FSH 5,3 (1,4-18,1 IU/L)
• LH 3,0 (1,5-9,3 IU/L)
• Prolactine 6,0 (2,1 17,7 ug/L)
• Testosterone 11,1 (8,4-28,7 nmol/l)
• Cortisol 347 nmol/l

10
Special investigations

• FBC Normal
• UE Urea 2,2 (2,6-7 mmol/l)
• LFT Normal
• Phosphate 1,48 (0,80-1,40 mmol/l)
• Glucose tolerance (mmol/l)
• 0 min 4,7 120 min
  8,6
• 30 min 7,0 150 min
  6,9
• 60 min 7,0 180 min
  5,5
• 90 min 7,2 210 min
  6,1

11
Special investigations

• Growth Hormone (expected random lt5,0mIU/l)
• Result gt 150
• Heartsonar LVUF 58
• L. Ventr.Hypertrophy

12

13

• Heel Pad Measurement
• Usually more than 22mm and must be
  measured with lateral RX

14
MR Brain 2,8 x 2,5 x 3 cm

15
What is acromegaly?

• Greek word for "extremities" and "enlargement
• Chronic metabolic disorder
• Abnormal production of growth hormone
• in adult bone and tissue
• Excessive growth first in the hands and feet
• Later enlargement of other body tissues bones
  of the face, jaw, and skull

16
Pituitary gland

• Anterior Lobe
• GH , Prolactin , ACTH
• TSH , FSH , LH

17
(No Transcript)
18
Causes of acromegaly

• Pituitary adenoma , secreting GH
• Rare form hypersecretion of GHRH from an ectopic
  source (pancreatic islet)
• Even more rare form nonpituitary GH secreting
  tumor (lung)

19

• Signs of acromegaly often develop so gradually
  that they go unnoticed for years or even decades

20
Symptoms and signs

• Facial changes Coarsening of features
  Prognathism Diastema (widely spaced teeth)
• Acral enlargement Increased ring and shoe sizes
  Hands become enlarged, moist and soft. Tufting
  of distal phalanges

21
Symptoms and signs

• Skin changes Generalized Thickening Increased
  sweating and oiliness
• Visceromegaly
• Neuropathies and Arthropathy Carpal Tunnel
  Syndrome Peripheral neuropathy, paresthesias
  Spinal Cord or nerve root compression from bony
  overgrowth Enlargement of bone

22

Acromegaly - marked kyphoscoliosis. X-rays showed
irregular
hypertrophy of vertebrae.
23
Symptoms and signs

• Local Effects of Pituitary (mass effect)
  Headache visual impairment
• Cardiovascular disease Cardiomyopathy left
  ventricular diastolic function decreased
  arrhythmia Hypertension

24

Acromegaly complete 3rd nerve palsy secondary to
tumour invasion.
25
Symptoms and signs

• Respiratory Disease Upper Airway Obstruction
  (Caused by Soft Tissue Overgrowth) Sleep Apnea
• Malignancy Colon

26
Symptoms and signs

• Endocrinopathy (due either to GH excess or to
  mechanical effects of the adenoma)
  Hyperprolactinemia Diabetes Mellitus/Carbohydrat
  e intolerance Hypogonadism Hypothyroidism
  Hypoadrenalism Decreased libido or impotence

27
Symptoms and signs

• General Systemic Manifestations Fatigue or
  lethargy Weight Gain Heat intolerance
  Photophobias Increased sleep requirement

28
(No Transcript)
29
Tests

• The normal level of serum GH is lt5,0mIU/l
• - A single measurement is not reliable
• An acromegalic may have normal GH levels
• Stress, sleeping time, exercise can increase GH
  up to 5 times

30
Tests

• Oral Glucose Tolerance Test (OGTT)
• This is the best test to confirm the disease.
  The simplest and most specific dynamic test. 75g
  of Glucose is administered after an overnight
  fast.
• Results can be Normal GH levels suppressed.
• Acromegalia GH levels paradoxically increased.

31
IGF-1

• Is an indirect measurement of GH.
• Measurement of choice IGF-1 shows less
  variation than growth hormone.
• Reliable indicator of disease activity

32

33
HGH

• GH secretion remains episodic BUT amplitude and
  number of secretory episodes are elevated.
• The characteristic nocturnal surge is absent.
• Abnormal responses to suppression.

34

35
Further investigations

• After laboratory confirmation of acromegaly,
  additional investigations can be done
• MRI Tumor Localization

36
Treatment

• 1. Surgical therapy
• This is the gold standard of GH-secreting tumors
  because of its aggressive behavior.
• Must be done as the primary choice in all
  patients

37
(No Transcript)
38
Treatment

• 2. Radiation therapy
• The disadvantage is the long-term duration to
  reach the goals of therapy.
• About 5 years are required for reduction of GH
  levels to normal in 50 of the patients.

39
Treatment

• 3. Conservative Therapy
• Two medications are currently used (Medical
  therapy is sometimes used to shrink large tumors
  before surgery)
• Dopaminergic Analogues eg. Bromocriptine
• Somatostatin analogues (Octreotide)

40
(No Transcript)
41
Follow-up

• Goals of therapy  GH normal
  Stabilization in tumor size
• Preservation of normal pituitary function
  
• Improvement in Clinical and metabolic parameters
• 6 monthly Physical, Biochemical and Radiology
  follow-up

42
Typical of Acromegaly

• GH secreting Pituitary adenomas are often gt 1cm
  in diameter.
• About 15 of GH secreting tumors also
  hypersecrete PRL resulting in the clinical
  manifestation of hyperprolactinemia.

43
Typical of Acromegaly

• No known risk factors for acromegaly other than a
  prior history of a pituitary tumor
• Consequences of GH excess Lifelong disease

44
Acromegaly Statistics

• Very rare condition.
• Develops between the ages of 30 and 50
• The mean age at diagnosis is 42 years
• Equal gender and ethnic incidence.
• Duration of symptoms 5-10 years before
  diagnosis.

45

46

Prominent supra-orbital ridge, jaw, and generally
enlarged facial features
47

48
                                               
             

Acromegaly marked prognathism ,
prominence of frontal bones
49

macroglossia
50

Acromegaly - gross disorganization of bone
architecture of feet.
51
Prognosis

• Pituitary surgery is successful in up to 90 of
  patients (tumor size dependant)
• Radiation therapy successful in reducing symptoms
  up to 70 of patients for ?5 years
• Without treatment, symptoms progress and
  cardiovascular disease increase

52
Acromegaly before closure of growth plates
53

Robert Pershing Wadlow (1918-1940) the Worlds
Tallest Man at 8 11.1
54
The future of acromegaly research

• Researchers are studying the genetics behind
  development of pituitary tumors
• Why the tumors develop in midlife?
• Pegvisomant (Somavert) is a manufactured protein
  simular to growth hormone. Binds to the same
  receptor and blocks the effect of growth hormone.
• FDA approved. Not available in SA

55
Thank you
56

• 1.  FITZGERALD, Paul. "Gigantism Acromegaly",
  Handbook of Clinical Endocrinology, 2nd ed.,
  Appleton Lange. Norwalk, Connecticut/ San
  Mateo, California, 1992, pp 50-56 2.
  ISSELBACHER, Kurt J., BRAUNWALD, Eugene., WILSON
  Jean D., MARTIN, Joseph B., FAUCI, Anthony S.,
  KASPER, Dennis L. "GH Phisiology", "GH
  excess", "Pituitary Adenoma", Harrison Internal
  Medicine. 2nd Vol, No 13, New York McGraw-Hill
  Book Company, 1994, pp 1990-1995 2002-206

57

• 3. GREENSPAN, Francis S., STREWLER, Gordon J.
  "Growth Hormone" and "Acromegaly Gigantism",
  Basic Clinical ENDOCRINOLOGY, 5th ed, Appleton
  Lange. 1997, pp 106-108 136-142 4. FROHMAN,
  Lawrence A . "Clinical Review 22 Therapeutic
  Options in Acromegaly". Journal of Clinical
  Endocrinology and Metabolism 1991 Vol 72 No 6,
  USA, pp 1175-1183

58

• 5. MELMED, Shlomo. "Unwanted Effects of Growth
  Hormone Excess in the Adult". Journal of
  Pediatric Endocrinology Metabolism 1996 Vol 9,
  Suppl. 3, London, pp 369-374 6. Acromegaly
  Therapy Consensus Development Painel. "Consensus
  Statement Benefits Versus Risks of Medical
  Therapy for Acromegaly". The American Journal of
  Medicine, 1994, november, Vol 97, pp 468-473

59

• 7. VAISMAN, M., AGUIAR, R., CIPRIANI, R.,
  VIOLANTE, A. H. D., ZAJDENVERG, L. "Acromegalia
  Familiar", Apresentaçao de Casos dos ABEM,
  Arquivos Brasileiros de Endocrinologia e
  metabologia, 1996 40/3 213-5) 8. FELIG, P
  BENTON, J.D. FROHMAN, L. A., "Endocrinoly and
  Metabolism", 3rd ed., 1995, pp 341-349

60

• 9. NIDDK, NIH Publication (The National Institute
  of Diabetes and Digestive and Kidney Diseases of
  the National Institute of Health) No. 95-3924,
  February 1995 (http//www.niddk.nih.gov/Acromegaly
  /Acromeg.html) 10. BESSER, G. Michael, MD,
  THORNER, Michael O "Cushings Syndrome",
  "Imaging of the pituitary and Hypothalamus".
  Clinical Endocrinology, 1994, 2nd ed, Wolfe, pp
  24.7-9.