Acromegaly - Clinical Round Presented by Usama Ragab Youssif For 5th-year Medical students - Zagazig University

1. Usama Ragab Youssif, MD
Consultant Internal Medicine
Lecturer of Medicine
Zagazig University
Email: usamaragab@medicine.zu.edu.eg
Slideshare: https://www.slideshare.net/dr4spring/
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Acromegaly
Clinical Implications & Summaries

2. Theoretical
The pituitary is the maestro

3. Anatomy of pituitary gland
 Size: 13 mm × 9 mm × 6 mm
 Weight: 50 – 100 mg
 It is a small oval gland situated at the base of the skull in the sella
turcica within the sphenoid bone.
 It consists of anterior pituitary & posterior pituitary.

4. Relations
 Anterior: Tuberculum sellae.
 Posterior: Dorsum sellae & brain stem.
 Inferior: Sphenoidal air sinus.
 Superior: Diaphragma sellae, optic
chiasma and hypothalamus.
 Lateral: cavernous sinus; within it lies
internal carotid artery, cranial nerves III,
IV, VI and ophthalmic and maxillary
branches of V cranial nerve.

8. Growth hormone (GH)
 Single chain polypeptide.
 Pulsatile secretion, usually undetectable in the serum, apart from 5
to 6 of 90 min pulses/24h that occur more commonly at night.
 The secretion is modified by age and sex.
 It is secreted by acidophil cells. There is structural similarity
between it and prolactin so it has a lactogenic activity.

9. Actions
Growth
Linear growth, increase tissue
size, growth of bone &Viscera.
Metabolic
Carbohydrate
↑ blood glucose i.e.
diabetogenic
Protien
Anabolic i.e. +ve
nitrogen balance
Fat
++ Mobilization of fat from
adipose tissue

10. Factors lead to stimulation of growth hormone
 Hypoglycemia (insulin stimulation test).
 Sleep.
 Protein excess.
 Arginine aminoacid.
 Glucagon.
 Clonidine

11. Factors lead to inhibition of growth hormone
 ↑ Blood glucose (glucose inhibition test).
 ↑ Cortisol.
 ↑ Free fatty acids.

12. Acromegaly pathophysiology
 Acromegaly is the clinical condition resulting from prolonged
excessive GH and hence IGF-1 secretion in adults.
 Loss of pulsatile nature of GH secretion and failure of GH to
become undetectable during the 24h day, unlike normal controls.
 It usually starts in the 4th and 5th decades & is mostly due to
acidophil adenoma.

13. Causes of acromegaly
 Pituitary adenoma (>99% of cases). Macroadenomas 60–80%,
microadenomas 20–40%. Local invasion is common.
 GHRH secretion:
 Hypothalamic secretion.
 Ectopic GHRH, e.g. carcinoid tumour (pancreas, lung) or other
neuroendocrine tumours.
 Ectopic GH secretion.

14. Clinical Picture
Rational
 Excess GH/IGF-1
 Excess PRL in some (as there is co-secretion of PRL in a minority
(30%) of tumours or, rarely, stalk compression)
 Tumour mass

15. Galactorrhea in case of acromegaly
 There is structural similarity
between it and prolactin
 There is co-secretion of PRL in
a minority (30%) of tumours
 Rarely, stalk compression

16. Clinical picture (cont.)
Facies
 (old photographs are frequently
useful); coarse facial features or
acromegalic facies
 Prominent supraorbital ridges,
big skull.
 Increased size of cartilage of ear,
broad nose.
 Prognathism with increased
interdental separation, large
tongue.

18. Clinical picture (cont.)
Hand, feet & joints: change in ring
or shoe size…
 Increased size of the hands
(spade like hands) with tight
rings, enlargement of feet.
 Degenerative changes in joints
lead to osteoarthritis → joint pain
with crepitus in joints.
Visceronmegaly:
 Goitre and other organomegaly—
liver, heart, kidney

19. Clinical picture (cont.)
Associated endocrinal disturbances:
 Hyperprolactinemia in 30% of patients that leads to hypogonadism,
and amenorrhea, galactorrhoea, poor libido and ED (prolactine
inhibits Gn)
 Diabetes: GH is diabetogenic (polyurea, polydipsia, polyphagia):
with insulin resistance
 Thyroid enlargement but thyrotoxicosis is rare.

20. Clinical picture (cont.)
Neuropsychiatric manifestations:
 Central: Pressure manifestations with pituitary tumors (e.g. bitemporal
hemianopia).
 Peripheral:
 Diabetic neuropathy, with tingling and numbness.
 Entrapment neuropathies e.g. carpal tunnel syndrome (in about
40%).
 Psychiatric: emotional instability, hypersomnolence.

22. Clinical picture (cont.)
Other manifestations:
 Headaches
 Tiredness, lethargy, muscle weakness (generalized myopathy).
 Hollow voice or deep voice (laryngeal hypertrophy).
 Thick skin and excessive sweating, oily or greasy skin, acanthosis
nigricans,weight gain, edema.

23. Complications
 Hypertension (40%).
 Insulin resistance and impaired glucose tolerance (40%)/diabetes
mellitus (20%).
 Obstructive sleep apnoea—due to soft tissue swelling in
nasopharyngeal region.
 Increased risk of colonic polyps and colonic carcinoma.

25. Complications (cont.)
 Ischaemic heart disease and cerebrovascular disease.
 Congestive cardiac failure
 Mass effect; tumor expansion
 Pituitary apoplexy—rapid expansion of a pituitary tumor due to
infarction or hemorrhage within the tumor. The patient may
complain of sudden severe headache followed by loss of
consciousness. Immediate neurosurgical intervention should be
done.

26. Workup
X-ray:
 Skull: thick cortex, enlarged paranasal sinuses, and prognathism
and widening of sella turcica.
 Hands: Tufting of terminal phalanges (mushroom appearance).
 Soft tissue: showing thickness of the heel pad (18 mm in females
and 21 mm in males).

30. Workup (cont.)
CT and MRI with pituitary
protocol: pituitary
macroadenoma.
 MRI usually demonstrates the
tumour (98%) and whether
there is extrasellar extension,
either suprasellar or into the
cavernous sinus.
 In 80% of cases it is
macroadenoma.

31. Workup (cont.)
Laboratory investigations:
 Oral glucose tolerance test (OGTT)
 An abnormal test is defined by a failure to suppress GH to <0.33
mcg/L (in response to a 75 g oral glucose load), as assessed by
GH measurements every 30 minutes over a 2-hour period.
 Random GH: not useful, we may use GH curve
 IGF-1
 IGF-1 is the single best screening test for acromegaly

32. Workup (cont.)
Laboratory investigations
(cont.):
 Pituitary function testing
 Serum PRL may be elevated
from stalk effect or GH/PRL
tumors’ cosecretion.
 In case of macroadenomas,
assess other anterior pituitary
hormones (e.g., free T4,
cortisol, testosterone or
estradiol) to exclude
hypopituitarism.

33. Workup (cont.)
 Visual field should be checked: perimetry
 Evaluate for comorbidities: Evaluate and treat potential comorbid
conditions, including:
 Impaired glucose intolerance/diabetes
 Dyslipidemia
 Sleep apnea
 Cardiac disease (baseline ECG and echocardiogram)
 Colonic polyps (colonoscopy).

34. Activity of the disease is determined by
 GH > 10 ng/ml with no response to glucose suppression.
 Increased IGF-1
 Hyperphosphatemia (due to increased tubular reabsorption by GH)
 Excessive sweating.

35. Management
 Surgical: Transphenoidal microsurgery
 Radiotherapy
 Medical
 Somatostatin analogues
 Dopamine agonists
 GH receptor antagonists (pegvisomant)

37. Clinical Wise
‫أكروميجالي‬ ‫حالة‬ ‫جاتلي‬ ‫لو‬ ‫اإلمتحان‬ ‫في‬ ‫إيه‬ ‫أعمل‬

38. Personal History
 N
 A = gigantism versus acromegaly
 S = male (macroadenoma) versus female (microadenoma)
 O
 M = married or divorced
 R
 H
 H

39. Chief complaint = ‫بالبلدي‬ ‫العيان‬ ‫كالم‬
 Pain
 Swelling
 Disturbance of function
+ duration

40. Endocrine Symptomatology
 Alteration in height, e.g. increase or decrease
 Weight gain or loss
 Polyuria and polydipsia
 Menstrual irregularity
 Thyroid swelling with or without signs of thyrotoxicosis
 Hypothyroidism or its features
 Gynaecomastia
 Hirsutism
 Myopathy or muscle weakness.

41. Example of Chief complaint in acromegaly
 Progressive enlargement of the body for … months
 Weakness and weight gain for … months
 Change in voice for … months
 Headache for … months
 Joint pain for … months
 Excessive sweating for … months.

42. Present history = ‫منمق‬ ‫طبي‬ ‫كالم‬
 Analysis of complain: Chronological order of symptoms, mode of
onset, their progression and course
 Analysis of symptoms of the same system = ‫نونو‬
 Ask for associated symptoms = ‫نونو‬
 Investigations done (related to symptoms)
 Treatment taken: e.g. replacement therapy or oral contraceptives.

43. Present history
 General = sweating + heat or cold intolerance + appetite
 CVS = symptoms of HF, HTN….
 Chest =
 NS = central or peripheral +/- psychiatric
 GIT = polypi

44. Example of Present history in acromegaly
 According to the statement of the patient, he was reasonably well
… years back. Since then, he has been experiencing progressive
enlargement of body, mainly his head, hands and feet. His face is
also enlarged, including the jaw, leading to difficulty in chewing. He
also complains of severe weakness despite significant weight gain.
His voice has recently changed and become hoarse.
 The patient also complains of frequent headache involving the
whole head, more marked in the morning, which is not associated
with nausea or vomiting.

45. Present history (cont.)
 For the last … months, he is also complaining of joint pain involving
both the knees, ankles and elbows. The pain is aggravated by
activity and relieved by taking rest. It is not associated with morning
stiffness. Recently he noticed excessive sweating even at rest.
There is no history of any visual disturbance, cold intolerance,
sleepiness. His bowel and bladder habits are normal.

46. Past History
 Drugs
 Operation: previous surgery or radiation
 Disease

47. Family history
 DM or any other endocrinal or autoimmune disease.
 Similar condition in the family = familial acromegaly

48. Sexual History
 Erectile dysfunction
 Loss of libido
 Dry ejaculation
 Galactorrhea
 Amenorrhea
 Irregular menses
 Dysfunctional uterine bleeding
 Details of pregnancies or PPH
in females
Menstrual & Obestetric
History

49. General examination
Vital signs General overview
 Pulse
 BP
 Temperature
 Respiratory rate
 Appearance
 Built
 Color
 Decubitus
 Exposure: back & genitalia
 Facial expression
 Gait
 Mental

50. General examination
Regional examination Systemic examination
 Head & Neck
 Upper limbs
 Lower limbs
 CVS
 Chest
 Abdomen
 CNS

51. General Examination
 Appearance, built, height, weight BMI and body proportions
 Face, e.g. periorbital oedema, moon-facies, prognathism, etc.
 Eyes, e.g. exophthalmos, proptosis, signs of Grave’s ophthalmopathy,
visual acuity
 Ear, e.g. deafness, size
 Mouth, e.g. large protruding tongue, thick lips, etc.
 Neck, e.g. goitre, carotid, pulsations/bruit, JVP.

52. Face
 Look at the face for
coarsening of features, thick,
greasy skin, prominent
supraorbital ridges,
enlargement of the nose,
prognathism (protrusion of the
mandible) and separation of
the lower teeth.
 Ask patient to open his mouth
and show his teeth

53. Upper & lower limbs
 Shake hands!!
 Examine the hands and feet
for soft-tissue enlargement
and tight-fitting rings or shoes,
carpal tunnel syndrome and
arthropathy
 Large feet

54. Visual field
 Bitemporal hemianopia

55. Genitalia & breasts
 Look genitalia for hyper or
hypogonadism
 Virilisation
 Breast development, atrophy
and galactorrhoea.

56. Systemic examination
CNS CVS
 Look for higher function,
cranial nerve, speech
 Look for abnormal movements
 Motor system examination for
brisk or delayed jerks or
myopathy
 Sensory system examination
for neuropathy including
carpal tunnel syndrome
 Look for cardiomegaly
 Auscultate for change in heart
rate, rhythm, murmur or any
other abnormal sound

57. Systemic examination
Muscloskeletal GIT
 Look for osteoporosis, crush
fractures or arthropathy
 Tongue
 Organomegaly
 Stria

58. Example of General examination in acromegaly
 The patient looks obese with large coarse face, large jaw with
widely apart teeth prominent supraorbital ridge, increased wrinkling
of the forehead and baggy eyelids. Nose, lips and ears are large
 Scalp is large (bulldog scalp)
 Hands are large, warm and sweaty with doughy feeling, fingers are
spade like
 Feet are large

59. General examination (cont.)
 Skin is thick, greasy, and sweaty (hyperhydrosis)
 Coarse body hair
 Voice is husky, cavernous
 Gynecomastia: Present
 Clubbing: Present (involving all fingers and toes)

60. General examination (cont.)
 Thyromegaly (diffusely enlarged)
 There is no anemia, jaundice, cyanosis, koilonychia, leukonychia,
edema
 There may be kyphosis, scoliosis, axillary skin tag, acanthosis
nigricans.

61. Example of Systemic examination in acromegaly
GIT Nervous system
 Tongue, lips and jaw are
enlarged. Lower jaw is
protruded with malocclusion of
teeth (prognathism).
 Abdomen—hepatomegaly
(may be).
 Voice is hoarse, husky and
cavernous.
 Visual field defect—bitemporal
hemianopia.

62. Systemic examination (cont.)
CVS Skeletal
 Cardiomegaly (evidenced by
shifting of the apex beat,
which is heaving).
 Both the knee and ankle
joints, elbow joints, also joints
of hands are tender, but no
restricted movement.

63. My diagnosis is
Acromegaly
Associated (complicated) with
diabete or HTN or whatever…

65. What are the changes in the eyes in
acromegaly?
 Visual field defect, usually bitemporal hemianopia (due to pressure
on optic chiasma).
 Others—optic atrophy, papilledema, angioid streaks in retina.

66. What are the causes of prominent supraorbital
ridge?
 Rickets
 Paget's disease
 Achrondroplasia
 Hydrocephalus
 Hereditary hemolytic anemia.

67. What are the causes of macroglossia?
 Acromegaly
 Hypothyroidism
 Amyloidosis
 Down's syndrome.

68. You are in the examination theatre

69. Many a times, examiner used to ask:
 ‘Look at the face. What is your diagnosis? What else do you want
to examine?’
 ‘Examine the neck of this patient.’
 ‘Perform the general examination’.
 ‘Examine the hands of this patient’.

70. Underlying diagnoses by looking at the face may
be:
 Graves’ disease (hyperthyroid, euthyroid or hypothyroid) or
thyrotoxicosis (due to any cause).
 Hypothyroidism (myxoedema).
 Cushing’s syndrome.
 Acromegaly.
 Pigmentation (in Addison’s disease).

71. Subsequent physical examination depends on
your diagnosis
 If your diagnosis is thyroid disease: further clinical examination will
be related to thyroid problems, e.g., signs of thyrotoxicosis, signs of
hypothyroidism, examination of the eye, thyroid gland etc.
 If your diagnosis is Cushing’s syndrome: examine other findings in
relation to this (central obesity, striae, proximal myopathy, blood
pressure).
 If acromegaly is suspected: then examine the face, hand, visual
field, voice.

72. Email: usamaragab@medicine.zu.edu.eg
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